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The cell biology of cell-in-cell structures

Nature Reviews Molecular Cell Biology volume 9, pages 796–809 (2008)Cite this article

Key Points

  • In mammalian systems, the internalization of one cell by another is most commonly associated with the phagocytic engulfment of apoptotic cells. However, alternative mechanisms of cell internalization also exist and, unlike phagocytosis, these alternative mechanisms target viable cells for internalization, forming what are referred to as cell-in-cell structures.

  • Cell-in-cell structures can form between various host and target cell types. Unlike apoptotic cells that are engulfed by phagocytosis and rapidly degraded, internalized cells within cell-in-cell structures remain viable for extended periods of time and exhibit various possible fates, including release or division inside the host, and cell death.

  • Although hundreds of reports document cell-in-cell phenomena occurring between diverse cell types, these structures can be generally grouped into two classes: those in which target cells internalize into hosts of different cell types (heterotypic cell-in-cell structures), which often occur between leukocyte target cells and non-leukocyte hosts, and those in which the target and host cell are of the same cell type (homotypic cell-in-cell structures), which often occur in human tumours.

  • Neither the mechanisms responsible for the generation of cell-in-cell structures nor their physiological roles are well understood. Based on existing data, we propose that these structures fall into three different groups that include both heterotypic and homotypic interactions: some structures seem to form transiently owing to normal or pathological transit of one cell through another (for example, transcellular migration of leukocytes), other structures might be generated to perform a specific physiological function (for example, for thymocyte maturation within thymic nurse cells), and other structures probably form fortuitously as a result of the admixture of adhesion-compatible cell types (for example, in human tumours).

  • Although these classifications begin to clarify the nature of these unusual cell structures, much remains to be understood regarding their physiological functions, including their more precise roles in haematopoietic cell maturation, or the consequences of cell-in-cell formation in human tumours, which exhibit both heterotypic and homotypic types of structures. That internalized cells and hosts exhibit various fates probably underscores the complex roles that these processes have in normal physiology and pathophysiology.

Abstract

For decades, authors have described unusual cell structures, referred to as cell-in-cell structures, in which whole cells are found in the cytoplasm of other cells. One well-characterized process that results in the transient appearance of such structures is the engulfment of apoptotic cells by phagocytosis. However, many other types of cell-in-cell structure have been described that involve viable non-apoptotic cells. Some of these structures seem to form by the invasion of one cell into another, rather than by engulfment. The mechanisms of cell-in-cell formation and the possible physiological roles of these processes will be discussed.

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Figure 1: Heterotypic internalization into non-neoplastic hosts.
Figure 2: Models of heterotypic cell-in-cell formation.
Figure 3: Homotypic cell internalization.
Figure 4: Model of homotypic cell internalization by entosis.

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References

  1. Eberth, J. Über die feineren bau der darmschleithaut. Wurzb. Naturwiss. Zeitschr. 5, 11 (1864) (in German).

    Google Scholar 

  2. Eimer, A. D. Zur beckerfrage. Virchow's Arch. 40, 282 (1867) (in German).

    Article  Google Scholar 

  3. von Arnstein, C. Über becherzellen und ihre beziehung zur fettresorption und sekretion. Arch. Mikrosk. Anat. 39, 527–547 (1867) (in German).

    Google Scholar 

  4. Paneth, J. Über die sezernierenden zellen der dünndarmepithels. Arch. F. Mikrosk. Anat. 31, 113–191 (1888) (in German).

    Article  Google Scholar 

  5. Bauchwitz, M. A. The bird's eye cell: cannibalism or abnormal division of tumor cells. Acta Cytol. Abstr. 25, 92 (1981).

    Google Scholar 

  6. Lewis, W. H. The engulfment of living blood cells by others of the same type. Anat. Rec. 31, 43–49 (1925). The first report to experimentally examine homotypic cell-in-cell structures to investigate the viability of internalized cells.

    Article  Google Scholar 

  7. Robertson, A. & Thomson, N. Morphology of programmed cell death in the ventral nerve cord of Caenorhabditis elegans larvae. J. Embryol. Exp. Morphol. 67, 89–100 (1982).

    Google Scholar 

  8. Fujinami, N., Zucker-Franklin, D. & Valentine, F. Interaction of mononuclear leukocytes with malignant melanoma. Lab. Invest. 45, 28–37 (1981). Showed the complete internalization of lymphocytes inside cultured metastatic melanoma cells by exclusion of ruthenium red from the internalized cell membrane.

    CAS  PubMed  Google Scholar 

  9. Ioachim, H. L. Emperipolesis of lymphoid cells in mixed cultures. Lab. Invest. 14, 1784–1794 (1965).

    CAS  PubMed  Google Scholar 

  10. Shamoto, M. Emperipolesis of hematopoietic cells in myelocytic leukemia. Electron microscopic and phase contrast microscopic studies. Virchow's Arch., B, Cell Pathol. 35, 283–290 (1981).

    Article  CAS  Google Scholar 

  11. Trowell, O. A. Intracellular lymphocytes in thymus reticular cells and in fibroblasts cultured in vitro. J. Physiol. 110, 5 (1949).

    Google Scholar 

  12. Trowell, O. A. The lymphocyte. Int. Rev. Cytol. 7, 236–286 (1958).

    Google Scholar 

  13. Sahebekhitiari, H. A. & Tavassoli, M. Marrow cell uptake by megakaryocytes in routine bone marrow smears during blood loss. Scand. J. Haematol. 16, 13–17 (1976). Examined a large panel of human bone marrow smears and correlated a high frequency of haematopoietic cell–megakaryocyte emperipolesis with blood loss.

    Article  CAS  PubMed  Google Scholar 

  14. Hughes, D. Invasion of neurones in vitro by non-immune lymphocytes. Br. J. Exp. Pathol. 48, 386–389 (1967).

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Klein, R. Ilots reticulo-lymphocytaires thymiques at spleniques foetaux humains et genese des mecanismes immunitaires. C. R. Seances. Soc. Biol. Fil. 156, 1623–1626 (1962) (in French).

    CAS  PubMed  Google Scholar 

  16. Dreyer, D. A., Shullenberger, C. C. & Dmochowski, L. A study on intracellular lymphocytes (“emperipolesis”) in tissue culture of lymph nodes from patients with malignant lymphoma. Tex. Rep. Biol. Med. 22, 61–69 (1964).

    CAS  PubMed  Google Scholar 

  17. Humble, J. G., Jayne, W. H. & Pulvertaft, R. J. Biological interaction between lymphocytes and other cells. Br. J. Haematol. 2, 283–294 (1956). Examined live lymphocytes internalized into various host cells in vitro by time-lapse microscopy, and coined the term emperipolesis, for “inside round about wandering”, to describe the long-term movements of internalized cells.

    Article  CAS  PubMed  Google Scholar 

  18. Koller, P. C. & Waymouth, C. Observations on intracellular leucocytes in tissue cultures of a rat tumour. J. R. Microsc. Soc. 72, 173–176 (1952).

    Article  CAS  PubMed  Google Scholar 

  19. Overholtzer, M. et al. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell 131, 966–979 (2007). Characterized a novel mechanism of cell-in-cell formation, termed entosis, whereby viable cells invade into their hosts using contractile force associated with adherens junction formation. Showed that entosis occurs in tumours in vivo and proposed that the process is tumour suppressive.

    Article  CAS  PubMed  Google Scholar 

  20. Pulvertaft, R. J. Cellular associations in normal and abnormal lymphocytes. Proc. R. Soc. Med. 52, 315–322 (1959).

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Tsunoda, R. et al. Emperipolesis of lymphoid cells by human follicular dendritic cells in vitro. Virchow's Arch., B, Cell Pathol. 62, 69–78 (1992).

    Article  CAS  Google Scholar 

  22. Lee, W. B., Erm, S. K., Kim, K. Y. & Becker, R. P. Emperipolesis of erythroblasts within Kupffer cells during hepatic hemopoiesis in human fetus. Anat. Rec. 256, 158–164 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Takeya, M. & Takahashi, K. Emperipolesis in a case of malignant lymphoma: electron microscopic and immunohistochemical investigation. Ultrastruct. Pathol. 12, 651–658 (1988).

    Article  CAS  PubMed  Google Scholar 

  24. Ioachim, H. & Furth, J. Intrareticular cell multiplication of leukemic lymphoblasts in thymic tissue cultures. J. Natl Cancer Inst. 32, 339–359 (1964).

    CAS  PubMed  Google Scholar 

  25. Andrew, W. & Andrew, N. V. Mitotic division and degeneration of lymphocytes within the cells of intestinal epithelium in the mouse. Anat. Rec. 9, 251–277 (1945).

    Article  Google Scholar 

  26. Andrew, W. & Sosa, J. M. Mitotic division and degeneration of lymphocytes within cells of intestinal epithelium in young and in adult white mice. Anat. Rec. 97, 63 (1947).

    Article  CAS  PubMed  Google Scholar 

  27. Wekerle, H., Ketelsen, U. P. & Ernst, M. Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: morphological and serological characterization. J. Exp. Med. 151, 925–944 (1980). This report and reference 30 were the first two reports to describe thymic nurse cells with internalized thymocytes, isolated from dissociated mouse and rat thymus tissue. Internalized thymocytes were viable and could be mitotic, and the authors speculated that they could be released from the host. These reports also showed that thymic nurse cells express MHC class I and II, and the authors speculated that these host cells play a role in thymocyte differentiation.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Andrew, W. & Collings, C. K. Lymphocytes within the cell of intestinal epithelium in man. Anat. Rec. 96, 445–457 (1946).

    Article  CAS  PubMed  Google Scholar 

  29. Benyesh-Melnick, M., Fernbach, D. J. & Lewis, R. T. Studies on human leukemia. I. Spontaneous lymphoblastoid transformation of fibroblastic bone marrow cultures derived from leukemic and nonleukemic children. J. Natl Cancer Inst. 31, 1311–1331 (1963).

    CAS  PubMed  Google Scholar 

  30. Wekerle, H. & Ketelsen, U. P. Thymic nurse cells—Ia-bearing epithelium involved in T-lymphocyte differentiation? Nature 283, 402–404 (1980).

    Article  CAS  PubMed  Google Scholar 

  31. Boll, I. T., Domeyer, C. & Buhrer, C. Human megakaryoblastic proliferation and differentiation events observed by phase-contrast cinematography. Acta Haematol. 97, 144–152 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Philp, D. et al. The binding, internalization, and release of thymocytes by thymic nurse cells. Cell. Immunol. 148, 301–315 (1993). Showed the dynamic interaction between thymocytes and thymic nurse cells in vitro by time-lapse microscopy, including the ability of internalized thymocytes to be released from the host.

    Article  CAS  PubMed  Google Scholar 

  33. Larsen, T. E. Emperipolesis of granular leukocytes within megakaryocytes in human hemopoietic bone marrow. Am. J. Clin. Pathol. 53, 485–489 (1970). First report to document megakaryocytes acting as hosts for viable internalized granular leukocytes, incuding neutrophils. Examined the interaction by time-lapse microscopy and found that an internalized cell could be released.

    Article  CAS  PubMed  Google Scholar 

  34. Ling, N. R., Acton, A. B., Roitt, I. M. & Doniach, D. Interaction of lymphocytes from immunized hosts with thyroid and other cells in culture. Br. J. Exp. Pathol. 46, 348–359 (1965).

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Tavassoli, M. Emperipolesis by megakaryocytes in blood loss. Br. J. Haematol. 49, 660–661 (1981).

    Article  CAS  PubMed  Google Scholar 

  36. Chemnitz, J. & Bichel, P. Tumour cell–tumour cell emperipolesis studied by transmission electron microscopy. Exp. Cell Res. 82, 319–324 (1973).

    Article  CAS  PubMed  Google Scholar 

  37. Shelton, E. & Dalton, A. J. Electron microscopy of emperipolesis. J. Biophys. Biochem. Cytol. 6, 513–514 (1959).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Klug, H. Über das vorkommen von lymphocyten in reticulumzellen. Experientia 18, 317–318 (1962) (in German).

    Article  CAS  PubMed  Google Scholar 

  39. Lee, K. P. Emperipolesis of hematopoietic cells within megakaryocytes in bone marrow of the rat. Vet. Pathol. 26, 473–478 (1989).

    Article  CAS  PubMed  Google Scholar 

  40. Lussier, C. et al. Cytology of Rosai–Dorfman disease. Diagn. Cytopathol. 24, 298–300 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. McClain, K. L., Natkunam, Y. & Swerdlow, S. H. Atypical cellular disorders. Hematology Am. Soc. Hematol. Educ. Program 2004, 283–296 (2004).

    Article  Google Scholar 

  42. von Andrian, U. H. & Mackay, C. R. T-cell function and migration. Two sides of the same coin. N. Engl. J. Med. 343, 1020–1034 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Marchesi, V. T. & Gowans, J. L. The migration of lymphocytes through the endothelium of venules in lymph nodes: an electron microscope study. Proc. R. Soc. Lond. B 159, 283–290 (1964). Documented, using serial electron microscopy, that lymphocytes can exit post capillary venules in vivo by traversing endothelial cell cytoplasm (transcellular migration), rather than by crossing between endothelial cell–cell junctions.

    Article  CAS  PubMed  Google Scholar 

  44. De Bruyn, P. P., Michelson, S. & Thomas, T. B. The migration of blood cells of the bone marrow through the sinusoidal wall. J. Morphol. 133, 417–437 (1971).

    Article  CAS  PubMed  Google Scholar 

  45. Farr, A. G. & De Bruyn, P. P. The mode of lymphocyte migration through postcapillary venule endothelium in lymph node. Am. J. Anat. 143, 59–92 (1975).

    Article  CAS  PubMed  Google Scholar 

  46. Becker, R. P. & De Bruyn, P. P. The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation. Am. J. Anat. 145, 183–205 (1976).

    Article  CAS  PubMed  Google Scholar 

  47. Carman, C. V. & Springer, T. A. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J. Cell Biol. 167, 377–388 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Engelhardt, B. & Wolburg, H. Mini-review: Transendothelial migration of leukocytes: through the front door or around the side of the house? Eur. J. Immunol. 34, 2955–2963 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Cernuda-Morollon, E. & Ridley, A. J. Rho GTPases and leukocyte adhesion receptor expression and function in endothelial cells. Circ. Res. 98, 757–767 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Azzali, G., Arcari, M. L. & Caldara, G. F. The “mode” of lymphocyte extravasation through HEV of Peyer's patches and its role in normal homing and inflammation. Microvasc. Res. 75, 227–237 (2008).

    Article  CAS  PubMed  Google Scholar 

  51. Carman, C. V. & Springer, T. A. Trans-cellular migration: cell–cell contacts get intimate. Curr. Opin. Cell Biol. 30 Jun 2008 (doi:10.1016/j.ceb.2008.05.007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Williamson, J. R. & Grisham, J. W. Leucocytic emigration from inflamed capillaries. Nature 188, 1203 (1960).

    Article  CAS  PubMed  Google Scholar 

  53. Williamson, J. R. & Grisham, J. W. Electron microscopy of leukocytic margination and emigration in acute inflammation in dog pancreas. Am. J. Pathol. 39, 239–256 (1961).

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Bobik, R. & Dabrowski, Z. Emperipolesis of marrow cells within megakaryocytes in the bone marrow of sublethally irradiated mice. Ann. Hematol. 70, 91–95 (1995).

    Article  CAS  PubMed  Google Scholar 

  55. Tavassoli, M. Modulation of megakaryocyte emperipolesis by phlebotomy: megakaryocytes as a component of marrow–blood barrier. Blood Cells 12, 205–216 (1986).

    CAS  PubMed  Google Scholar 

  56. Dzieciol, J. et al. Megakaryocytes in the acute stage of experimental hemorrhagic shock. Part II. Megakaryocytic regulation of cell release from the bone marrow. Rocz. Akad. Med. Bialymst. 40, 94–98 (1995).

    CAS  PubMed  Google Scholar 

  57. Weiss, L. The structure of bone marrow. Functional interrelationships of vascular and hematopoietic compartments in experimental hemolytic anemia: an electron microscopic study. J. Morphol. 117, 467–537 (1965).

    Article  CAS  PubMed  Google Scholar 

  58. Weiss, L. Transmural cellular passage in vascular sinuses of rat bone marrow. Blood 36, 189–208 (1970).

    Article  CAS  PubMed  Google Scholar 

  59. Thiele, J., Krech, R., Choritz, H. & Georgii, A. Emperipolesis—a peculiar feature of megakaryocytes as evaluated in chronic myeloproliferative diseases by morphometry and ultrastructure. Virchow's Arch., B, Cell Pathol. 46, 253–263 (1984).

    Article  CAS  Google Scholar 

  60. Behnke, O. An electron microscope study of the megacaryocyte of the rat bone marrow. I. The development of the demarcation membrane system and the platelet surface coat. J. Ultrastruct. Res. 24, 412–433 (1968).

    Article  CAS  PubMed  Google Scholar 

  61. Breton-Gorius, J. On the alleged phagocytosis by megakaryocytes. Br. J. Haematol. 47, 635–636 (1981).

    Article  CAS  PubMed  Google Scholar 

  62. Tefferi, A. Pathogenesis of myelofibrosis with myeloid metaplasia. J. Clin. Oncol. 23, 8520–8530 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. Schmitt, A. et al. Polymorphonuclear neutrophil and megakaryocyte mutual involvement in myelofibrosis pathogenesis. Leuk. Lymphoma 43, 719–724 (2002).

    Article  PubMed  Google Scholar 

  64. Schmitt, A. et al. Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in myelofibrosis. Blood 96, 1342–1347 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Falik-Zaccai, T. C. et al. A new genetic isolate of gray platelet syndrome (GPS): clinical, cellular, and hematologic characteristics. Mol. Genet. Metab. 74, 303–313 (2001).

    Article  CAS  PubMed  Google Scholar 

  66. Centurione, L. et al. Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1(low) mice. Blood 104, 3573–3580 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Novak, E. K. et al. Inherited thrombocytopenia caused by reduced platelet production in mice with the gunmetal pigment gene mutation. Blood 85, 1781–1789 (1995).

    Article  CAS  PubMed  Google Scholar 

  68. McGarry, M. P. et al. Increased incidence and analysis of emperipolesis in megakaryocytes of the mouse mutant gunmetal. Exp. Mol. Pathol. 66, 191–200 (1999).

    Article  CAS  PubMed  Google Scholar 

  69. Stenberg, P. E., McDonald, T. P. & Jackson, C. W. Disruption of microtubules in vivo by vincristine induces large membrane complexes and other cytoplasmic abnormalities in megakaryocytes and platelets of normal rats like those in human and Wistar Furth rat hereditary macrothrombocytopenias. J. Cell Physiol. 162, 86–102 (1995).

    Article  CAS  PubMed  Google Scholar 

  70. Jackson, C. W. et al. The Wistar Furth rat: an animal model of hereditary macrothrombocytopenia. Blood 71, 1676–1686 (1988).

    Article  CAS  PubMed  Google Scholar 

  71. Leven, R. M. & Tablin, F. Megakaryocyte and platelet ultrastructure in the Wistar Furth rat. Am. J. Pathol. 132, 417–426 (1988).

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Dipasquale, B. & Tridente, G. Immunohistochemical characterization of nurse cells in normal human thymus. Histochemistry 96, 499–503 (1991).

    Article  CAS  PubMed  Google Scholar 

  73. Ritter, M. A., Sauvage, C. A. & Cotmore, S. F. The human thymus microenvironment: in vivo identification of thymic nurse cells and other antigenically-distinct subpopulations of epithelial cells. Immunology 44, 439–446 (1981).

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Penit, C. In vivo thymocyte maturation. BUdR labeling of cycling thymocytes and phenotypic analysis of their progeny support the single lineage model. J. Immunol. 137, 2115–2121 (1986).

    CAS  PubMed  Google Scholar 

  75. Webb, O. et al. The identification of thymic nurse cells in vivo and the role of cytoskeletal proteins in thymocyte internalization. Cell. Immunol. 228, 119–129 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Pezzano, M., Samms, M., Martinez, M. & Guyden, J. Questionable thymic nurse cell. Microbiol. Mol. Biol. Rev. 65, 390–403 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Sandilands, G. P., Reid, F. M., Gray, K. G. & Anderson, J. R. Lymphocyte emperipolesis revisited. I. Development of in vitro assay and preliminary characterisation of the lymphocyte subpopulation involved. Immunology 35, 381–389 (1978).

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Reid, F. M., Sandilands, G. P., Gray, K. G. & Anderson, J. R. Lymphocyte emperipolesis revisited. II. Further characterization of the lymphocyte subpopulation involved. Immunology 36, 367–372 (1979).

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Tanaka, M., Aze, Y. & Fujita, T. Adhesion molecule LFA-1/ICAM-1 influences on LPS-induced megakaryocytic emperipolesis in the rat bone marrow. Vet. Pathol. 34, 463–466 (1997).

    Article  CAS  PubMed  Google Scholar 

  80. Lindhout, E., Lakeman, A., Mevissen, M. L. & de Groot, C. Functionally active Epstein-Barr virus-transformed follicular dendritic cell-like cell lines. J. Exp. Med. 179, 1173–1184 (1994).

    Article  CAS  PubMed  Google Scholar 

  81. Yang, L. et al. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow. Blood 106, 584–592 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Lugini, L. et al. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer Res. 66, 3629–3638 (2006). Showed that internalization of live T cells can increase the survival of metastatic melanoma host cells under starvation conditions.

    Article  CAS  PubMed  Google Scholar 

  83. Fais, S. Cannibalism: a way to feed on metastatic tumors. Cancer Lett. 258, 155–164 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Millan, J. et al. Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains. Nature Cell Biol. 8, 113–123 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Heiska, L. et al. Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate. J. Biol. Chem. 273, 21893–21900 (1998).

    Article  CAS  PubMed  Google Scholar 

  86. Schnitzer, J. E., Oh, P., Pinney, E. & Allard, J. Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J. Cell Biol. 127, 1217–1232 (1994).

    Article  CAS  PubMed  Google Scholar 

  87. Yamada, S. & Nelson, W. J. Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell–cell adhesion. J. Cell Biol. 178, 517–527 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Liebman, E. The function of leucocytes in the growth and regression of the egg of Triturus viridescens. Am. J. Anat. 77, 273 (1945).

    Article  Google Scholar 

  89. Ioachim, H. L. Emperipolesis of lymphoid cells in mixed cultures. Proc. Am. Assoc. Cancer Res. 6, 32 (1965).

    Google Scholar 

  90. Tinari, A., Matarrese, P., Minetti, M. & Malorni, W. Hyperphagia by self- and xeno-cannibalism: cell death by indigestion?: a reminiscence of the Phedrus Fabula “Rana Rupta et Bos”? Autophagy 4, 128–130 (2008).

    Article  PubMed  Google Scholar 

  91. Nishie, M. et al. Oligodendrocytes within astrocytes (“emperipolesis”) in the cerebral white matter in hepatic and hypoglycemic encephalopathy. Neuropathology 26, 62–65 (2006).

    Article  PubMed  Google Scholar 

  92. Wu, E. & Raine, C. S. Multiple sclerosis. Interactions between oligodendrocytes and hypertrophic astrocytes and their occurrence in other, nondemyelinating conditions. Lab. Invest. 67, 88–99 (1992).

    CAS  PubMed  Google Scholar 

  93. Shintaku, M. & Yutani, C. Oligodendrocytes within astrocytes (“emperipolesis”) in the white matter in Creutzfeldt-Jakob disease. Acta Neuropathol. 108, 201–206 (2004).

    Article  PubMed  Google Scholar 

  94. de Pasquale, A., Paterlini, P., Quaglino, D. & Quaglino, D. Emperipolesis of granulocytes within megakaryocytes. Br. J. Haematol. 60, 384–386 (1985).

    Article  CAS  PubMed  Google Scholar 

  95. Pezzano, M. et al. Thymic nurse cell rescue of early CD4+CD8+ thymocytes from apoptosis. Cell. Mol. Biol. (Noisy-le-grand) 41, 1099–1111 (1995).

    CAS  PubMed  Google Scholar 

  96. Martinez, M. et al. Thymic nurse cell multicellular complexes in HY-TCR transgenic mice demonstrate their association with MHC restriction. Exp. Biol. Med. (Maywood) 232, 780–788 (2007).

    CAS  Google Scholar 

  97. van de Wijngaert, F. P., Rademakers, L. H., Schuurman, H. J., de Weger, R. A. & Kater, L. Identification and in situ localization of the “thymic nurse cell” in man. J. Immunol. 130, 2348–2351 (1983).

    CAS  PubMed  Google Scholar 

  98. Hiramine, C., Nakagawa, T., Miyauchi, A. & Hojo, K. Thymic nurse cells as the site of thymocyte apoptosis and apoptotic cell clearance in the thymus of cyclophosphamide-treated mice. Lab. Invest. 75, 185–201 (1996).

    CAS  PubMed  Google Scholar 

  99. Schwartz, R. H. Acquisition of immunologic self-tolerance. Cell 57, 1073–1081 (1989).

    Article  CAS  PubMed  Google Scholar 

  100. Tsunoda, R. et al. Human follicular dendritic cells in vitro and follicular dendritic-cell-like cells. Cell Tissue Res. 288, 381–389 (1997).

    Article  CAS  PubMed  Google Scholar 

  101. Tsunoda, R., Heinen, E. & Sugai, N. Follicular dendritic cells in vitro modulate the expression of Fas and Bcl-2 on germinal center B cells. Cell Tissue Res. 299, 395–402 (2000).

    Article  CAS  PubMed  Google Scholar 

  102. Moore, A. E. & Hlinka, J. Activities of lymphocytes inside fibroblasts. Proc. Am. Assoc. Cancer Res. 5, 46 (1964).

    Google Scholar 

  103. Sinkovics, J. G. Intracellular lymphocytes in leukaemia. Nature 196, 80–81 (1962).

    Article  CAS  PubMed  Google Scholar 

  104. Sinkovics, J. G., Shullenberger, C. C. & Howe, C. D. Cell destruction by lymphocytes. Lancet 287, 1215–1216 (1966).

    Article  Google Scholar 

  105. Hughes, D., Raine, C. S. & Field, E. J. Invasion of neurones in vitro by non immune lymphocytes. An electron microscopic study. Br. J. Exp. Pathol. 49, 356–359 (1968).

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Xia, P., Wang, S., Guo, Z. & Yao, X. Emperipolesis, entosis and beyond: dance with fate. Cell Res. 18, 705–707 (2008).

    Article  CAS  PubMed  Google Scholar 

  107. Radosevic, K. et al. Occurrence and a possible mechanism of penetration of natural killer cells into K562 target cells during the cytotoxic interaction. Cytometry 20, 273–280 (1995).

    Article  CAS  PubMed  Google Scholar 

  108. Burns, E. R., Zucker-Franklin, D. & Valentine, F. Characterization of the cell population mediating cytotoxicity and emperipolesis in human malignant melanomas. Trans. Assoc. Am. Physicians 94, 366–371 (1981).

    CAS  PubMed  Google Scholar 

  109. Pihl, E., Nind, A. P. & Nairn, R. C. Electron microscope observations of the in vitro interaction between human leucocytes and cancer cells. Aust. J. Exp. Biol. Med. Sci. 52, 737–743 (1974).

    Article  CAS  PubMed  Google Scholar 

  110. Wang, X. & Li, W. Mechanisms of natural killer cell-mediated tumor cell cytolysis at a single cell level. J. Med. Coll. PLA 2, 107–117 (1987).

    CAS  Google Scholar 

  111. Burns, E. R., Zucker-Franklin, D. & Valentine, F. Cytotoxicity of natural killer cells: correlation with emperipolesis and surface enzymes. Lab. Invest. 47, 99–107 (1982).

    CAS  PubMed  Google Scholar 

  112. Saxena, S., Beena, K. R., Bansal, A. & Bhatnagar, A. Emperipolesis in a common breast malignancy. A case report. Acta Cytol. 46, 883–886 (2002).

    Article  PubMed  Google Scholar 

  113. Ng, Y. K. & Ling, E. A. Emperipolesis of lymphoid cells in vagal efferent neurons following an intraneural injection of ricin into the vagus nerve in rats. Neurosci. Lett. 270, 153–156 (1999).

    Article  CAS  PubMed  Google Scholar 

  114. Brouwer, M., de Ley, L., Feltkamp, C. A., Elema, J. & Jongsma, A. P. Serum-dependent “cannibalism” and autodestruction in cultures of human small cell carcinoma of the lung. Cancer Res. 44, 2947–2951 (1984). Showed an engulfment process termed cannibalism that limited the survival of lung tumour explants in vitro , and also occurred in tumours in vivo . It also proposed that engulfment was a tumour-suppressive process.

    CAS  PubMed  Google Scholar 

  115. Shelton, E. & Rice, M. Studies on mouse lymphomas. III. Behavior of tumor- and non-tumor-cell populations during growth of three ascites lymphomas. J. Natl Cancer Inst. 21, 163–191 (1958).

    CAS  PubMed  Google Scholar 

  116. Domingo-Claros, A. et al. Oligoblastic leukaemia with (8;21) translocation and haemophagocytic syndrome and granulocytic cannibalism. Leuk. Res. 20, 517–521 (1996).

    Article  CAS  PubMed  Google Scholar 

  117. Jin, J. & Woodgett, J. R. Chronic activation of protein kinase Bβ/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: events associated with tumorigenesis. Oncogene 24, 5459–5470 (2005).

    Article  CAS  PubMed  Google Scholar 

  118. Terui, T. et al. The production of transforming growth factor-β in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. Blood 75, 1540–1548 (1990).

    Article  CAS  PubMed  Google Scholar 

  119. Bratton, D. L. & Henson, P. M. Apoptotic cell recognition: will the real phosphatidylserine receptor(s) please stand up? Curr. Biol. 18, R76–R79 (2008).

    Article  CAS  PubMed  Google Scholar 

  120. Park, D. et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450, 430–434 (2007).

    Article  CAS  PubMed  Google Scholar 

  121. Park, S. Y. et al. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 15, 192–201 (2008).

    Article  CAS  PubMed  Google Scholar 

  122. Miyanishi, M. et al. Identification of Tim4 as a phosphatidylserine receptor. Nature 450, 435–439 (2007).

    Article  CAS  PubMed  Google Scholar 

  123. Ravichandran, K. S. & Lorenz, U. Engulfment of apoptotic cells: signals for a good meal. Nature Rev. Immunol. 7, 964–974 (2007).

    Article  CAS  Google Scholar 

  124. Shelton, E. & Rice, M. Studies on mouse lymphomas. II. Behavior of three lymphomas in diffusion chambers in relation to their invasive capacity in the host. J. Natl Cancer Inst. 21, 137–161 (1958).

    CAS  PubMed  Google Scholar 

  125. Dey, P., Amir, T., Jogai, S. & Al Jussar, A. Fine-needle aspiration cytology of metastatic transitional cell carcinoma. Diagn. Cytopathol. 32, 226–228 (2005).

    Article  PubMed  Google Scholar 

  126. Fischer, A. & Dolschansky, L. Uber das wachstum von milzstromazellen in vitro. Arch. Entwmech.Org. 116, 123 (1929).

    Article  Google Scholar 

  127. Loreti, F. Z. Nuove ricerche ed osservazioni sulla migrazione di cellule linfoidi attraverso il tessuto epiteliale. (Nota II — La migrazione linfoide nell'epitelio del canalicolo renale nei pesci teleostei, ed il fenomeno della cario-anabiosi del Guieysse-Pellissier). Anat. Embryol. 103, 679–693 (1934).

    Google Scholar 

  128. Rosin, A. & Doljanski, L. Erythrocytes in the cytoplsm and nuclei of liver cells. Br. J. Exp. Pathol. 25, 111–115 (1944).

    CAS  PubMed Central  Google Scholar 

  129. Pulvertaft, R. J. & Humble, J. G. Intracellular phase of existence of lymphycotes during remission of acute lymphatic leukaemia. Nature 194, 194–195 (1962).

    Article  CAS  PubMed  Google Scholar 

  130. Wheatley, D. N. Cellular engulfment of erythrocytes. Br. J. Exp. Pathol. 49, 541–543 (1968).

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Halil, O. & Barrett, A. J. Phagocytosis by megakaryocytes in malignant disorders. Br. J. Haematol. 46, 161 (1980).

    Article  CAS  PubMed  Google Scholar 

  132. Djaldetti, M. & Strauss, Z. Emperipolesis by megakaryocytes in patients with non-Hodgkin's lymphoma and megaloblastic anemia. J. Submicrosc. Cytol. 14, 407–413 (1982).

    CAS  PubMed  Google Scholar 

  133. de Waal Malefijt, R., Leene, W., Roholl, P. J., Wormmeester, J. & Hoeben, K. A. T cell differentiation within thymic nurse cells. Lab. Invest. 55, 25–34 (1986).

    CAS  PubMed  Google Scholar 

  134. Tsunoda, R. et al. Immunohistochemical study on cultured FDC-C enriched lymphoid cell populations. Adv. Exp. Med. Biol. 237, 177–180 (1988).

    Article  CAS  PubMed  Google Scholar 

  135. Lindhout, E., Mevissen, M. L., Kwekkeboom, J., Tager, J. M. & de Groot, C. Direct evidence that human follicular dendritic cells (FDC) rescue germinal centre B cells from death by apoptosis. Clin. Exp. Immunol. 91, 330–336 (1993).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  136. Dzieciol, J. et al. [Phenomenon of emperipolesis of bone marrow megakaryocytes in experimental hemorrhage shock in rats]. Acta Haematol. Pol. 25, 165–169 (1994) (in Polish).

    CAS  PubMed  Google Scholar 

  137. Samms, M. et al. Lysosomal-mediated degradation of apoptotic thymocytes within thymic nurse cells. Cell. Immunol. 197, 108–115 (1999).

    Article  CAS  PubMed  Google Scholar 

  138. Avci, Z. et al. Thrombocytopenia and emperipolesis in a patient with hepatitis A infection. Pediatr. Hematol. Oncol. 19, 67–70 (2002).

    Article  PubMed  Google Scholar 

  139. Woulfe, D. S. et al. Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice. Blood 111, 3458–3467 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  140. Richters, A., Sherwin, R. P. & Richters, V. The lymphocyte and human lung cancers. Cancer Res. 31, 214–222 (1971).

    CAS  PubMed  Google Scholar 

  141. DeSimone, P. A., East, R. & Powell, R. D. Jr. Phagocytic tumor cell activity in oat cell carcinoma of the lung. Hum. Pathol. 11, 535–539 (1980).

    CAS  PubMed  Google Scholar 

  142. Ino, T., Hirano, M. & Shamoto, M. Emperipolesis observed in immature cells in blast crisis of chronic myelogenous leukaemia. Scand. J. Haematol. 26, 91–96 (1981).

    Article  CAS  PubMed  Google Scholar 

  143. Kamiyama, R., Onozawa, Y., Yamaguchi, H. & Tsukada, T. Emperipolesis and annulate lamellae in erythroleukaemia. Scand. J. Haematol. 30, 331–336 (1983).

    Article  CAS  PubMed  Google Scholar 

  144. Bacchi, C. E., Dorfman, R. F., Hoppe, R. T., Chan, J. K. & Warnke, R. A. Metastatic carcinoma in lymph nodes simulating “syncytial variant” of nodular sclerosing Hodgkin's disease. Am. J. Clin. Pathol. 96, 589–593 (1991).

    Article  CAS  PubMed  Google Scholar 

  145. Caruso, R. A., Famulari, C., Giuffre, G. & Mazzeo, G. Pleomorphic carcinoma of the gallbladder: report of a case. Tumori 77, 523–526 (1991).

    Article  CAS  PubMed  Google Scholar 

  146. Chetty, R. & Cvijan, D. Giant (bizarre) cell variant of renal carcinoma. Histopathology 30, 585–587 (1997).

    Article  CAS  PubMed  Google Scholar 

  147. Skinnider, L. F., Pabello, P. & Zheng, C. Y. Characteristics of a cell line established from a case of acute megakaryoblastic leukemia. Acta Haematol. 98, 26–31 (1997).

    Article  CAS  PubMed  Google Scholar 

  148. Kinkor, Z., Mukensnabl, P. & Michal, M. Inflammatory myxohyaline tumor with massive emperipolesis. Pathol. Res. Pract 198, 639–642 (2002).

    Article  Google Scholar 

  149. Shen, R. & Wen, P. Clear cell renal cell carcinoma with syncytial giant cells: a case report and review of the literature. Arch. Pathol. Lab. Med. 128, 1435–1438 (2004).

    Article  PubMed  Google Scholar 

  150. Khayyata, S., Basturk, O. & Adsay, N. V. Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils. Mod. Pathol. 18, 1504–1511 (2005).

    Article  PubMed  Google Scholar 

  151. Yasunaga, M. et al. Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung. Pathol. Int. 58, 244–248 (2008).

    Article  PubMed  Google Scholar 

  152. Burns, E. R. Tumor cell–tumor cell emperipolesis. Exp. Cell Res. 48, 229–231 (1967).

    Article  CAS  PubMed  Google Scholar 

  153. Chemnitz, J., Skaaring, P. & Bichel, P. Light and electron microscopy of the JB-1 ascites tumor at different stages of growth. Z. Krebsforsch. Klin. Onkol. Cancer Res. Clin. Oncol. 82, 111–131 (1974).

    Article  CAS  PubMed  Google Scholar 

  154. Chemnitz, J. & Skaaring, P. Increasing occurence of tumour cell — tumour cell emperipolesis in the regenerating JB-1 ascites tumour. Z. Krebsforsch. Klin. Onkol. Cancer Res. Clin. Oncol. 84, 89–96 (1975).

    Article  CAS  PubMed  Google Scholar 

  155. Chemnitz, J. & Skaaring, P. Tumor cell interactions in vitro microtubules, 100 Å filaments, and contractile microfilaments of tumor cells involved in “emperipolesis”. Z. Krebsforsch. Klin. Onkol. Cancer Res. Clin. Oncol. 92, 287–293 (1978).

    Article  CAS  PubMed  Google Scholar 

  156. Chemnitz, J. & Skaaring, P. Tumour cell interactions in vitro. Evidence for the occurrence of tumour cells within other tumour cells. Virchow's Arch., B, Cell Pathol. 28, 87–91 (1978).

    Article  CAS  Google Scholar 

  157. Masukawa, T. & Friedrich, E. G. Jr. Cytopathology of Paget's disease of the vulva. Diagnostic abrasive cytology. Acta Cytol. 22, 476–478 (1978).

    CAS  PubMed  Google Scholar 

  158. Towers, K. J. & Melamed, M. R. Absence of prognostic features in the cytology of effusions due to mammary cancer. Acta Cytol. 23, 30–34 (1979).

    CAS  PubMed  Google Scholar 

  159. Uei, Y., Watanabe, Y., Hirota, T., Yamamoto, H. & Watanabe, H. Cytologic diagnosis of breast carcinoma with nipple discharge: special significance of the spherical cell cluster. Acta Cytol. 24, 522–528 (1980).

    CAS  PubMed  Google Scholar 

  160. Frable, W. J., Bonfiglio, T. A., Kaminsky, D. B. & Murphy, W. M. Diagnostic cytology seminar. Acta Cytol. 24, 90–136 (1980).

    CAS  PubMed  Google Scholar 

  161. Hong, J. S. The exfoliative cytology of endometrial stromal sarcoma in peritoneal fluid. Acta Cytol. 25, 277–281 (1981).

    CAS  PubMed  Google Scholar 

  162. Craig, I. D., Desrosiers, P. & Lefcoe, M. S. Giant-cell carcinoma of the lung. A cytologic study. Acta Cytol. 27, 293–298 (1983).

    CAS  PubMed  Google Scholar 

  163. Ehya, H. The cytologic diagnosis of mesothelioma. Semin. Diagn. Pathol. 3, 196–203 (1986).

    CAS  PubMed  Google Scholar 

  164. Silverman, J. F., Dabbs, D. J., Finley, J. L. & Geisinger, K. R. Fine-needle aspiration biopsy of pleomorphic (giant cell) carcinoma of the pancreas. Cytologic, immunocytochemical, and ultrastructural findings. Am. J. Clin. Pathol. 89, 714–720 (1988).

    Article  CAS  PubMed  Google Scholar 

  165. Silverman, J. F., Finley, J. L., Berns, L. & Unverferth, M. Significance of giant cells in fine-needle aspiration biopsies of benign and malignant lesions of the pancreas. Diagn. Cytopathol. 5, 388–391 (1989).

    Article  CAS  PubMed  Google Scholar 

  166. Gupta, R. K. & Wakefield, S. J. Needle aspiration cytology, immunocytochemistry, and electron microscopic study of unusual pancreatic carcinoma with pleomorphic giant cells. Diagn. Cytopathol. 8, 522–527 (1992).

    Article  CAS  PubMed  Google Scholar 

  167. Stevens, M. W., Leong, A. S., Fazzalari, N. L., Dowling, K. D. & Henderson, D. W. Cytopathology of malignant mesothelioma: a stepwise logistic regression analysis. Diagn. Cytopathol. 8, 333–341 (1992).

    Article  CAS  PubMed  Google Scholar 

  168. Abati, A., Cajigas, A. & Hijazi, Y. M. Metastatic epithelioid hemangioendothelioma in a pleural effusion: diagnosis by cytology. Diagn. Cytopathol. 11, 64–67 (1994).

    Article  CAS  PubMed  Google Scholar 

  169. Nakajima, T. et al. Multivariate statistical analysis of bile cytology. Acta Cytol. 38, 51–55 (1994).

    CAS  PubMed  Google Scholar 

  170. Kojima, S., Sekine, H., Fukui, I. & Ohshima, H. Clinical significance of “cannibalism” in urinary cytology of bladder cancer. Acta Cytol. 42, 1365–1369 (1998).

    Article  CAS  PubMed  Google Scholar 

  171. Yokoo, H. et al. Retroperitoneal epithelioid angiomyolipoma leading to fatal outcome. Pathol. Int. 50, 649–654 (2000).

    Article  CAS  PubMed  Google Scholar 

  172. Kumar, P. V., Hosseinzadeh, M. & Bedayat, G. R. Cytologic findings of medulloblastoma in crush smears. Acta Cytol. 45, 542–546 (2001).

    Article  CAS  PubMed  Google Scholar 

  173. Demir, M. A., Ryd, W., Aldenborg, F. & Holmang, S. Cytopathological expression of different types of urothelial carcinoma in situ in urinary bladder washings. BJU Int. 92, 906–910 (2003).

    Article  CAS  PubMed  Google Scholar 

  174. Gupta, K. & Dey, P. Cell cannibalism: diagnostic marker of malignancy. Diagn. Cytopathol. 28, 86–87 (2003).

    Article  PubMed  Google Scholar 

  175. Lugini, L. et al. Potent phagocytic activity discriminates metastatic and primary human malignant melanomas: a key role of ezrin. Lab. Invest. 83, 1555–1567 (2003).

    Article  CAS  PubMed  Google Scholar 

  176. Ng, W. K. et al. Thin-layer cytology findings of small cell carcinoma of the lower female genital tract. Review of three cases with molecular analysis. Acta Cytol. 47, 56–64 (2003).

    Article  PubMed  Google Scholar 

  177. Gu, M., Ghafari, S. & Lin, F. Pap smears of patients with extramammary Paget's disease of the vulva. Diagn. Cytopathol. 32, 353–357 (2005).

    Article  PubMed  Google Scholar 

  178. Ylagan, L. R. & Zhai, J. The value of ThinPrep and cytospin preparation in pleural effusion cytological diagnosis of mesothelioma and adenocarcinoma. Diagn. Cytopathol. 32, 137–144 (2005).

    Article  PubMed  Google Scholar 

  179. Abodief, W. T., Dey, P. & Al-Hattab, O. Cell cannibalism in ductal carcinoma of breast. Cytopathology 17, 304–305 (2006).

    Article  CAS  PubMed  Google Scholar 

  180. Hattori, M. et al. Cell cannibalism and nucleus-fragmented cells in voided urine: useful parameters for cytologic diagnosis of low-grade urothelial carcinoma. Acta Cytol. 51, 547–551 (2007).

    Article  PubMed  Google Scholar 

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Acknowledgements

We apologize to those authors whose work was not referenced here. We thank E. S. Cibas for critical reading of the manuscript.

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  1. Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Michael Overholtzer

  2. Department of Cell Biology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Joan S. Brugge

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Glossary

Extravasate

The action of a cell (for example, a leukocyte or tumour cell) passing out of a vessel through an endothelial cell layer to enter into a tissue.

Demarcation membrane system

A large membrane network in the cytoplasm of megakaryocytes that is formed by tubular invagination of the plasma membrane and is proposed to be the source of proplatelet membranes.

α-granules

Secretory granules that are found in megakaryocytes and platelets and contain growth factors, clotting factors and the adhesion molecule P-selectin.

Thymic cortex

The outer region of the thymus that contains large numbers of immature thymocytes, in which early events in T-cell development occur, including positive and negative selection.

Uropod

A tail structure that is characteristic of certain types of polarized migrating cells, such as lymphocytes.

FERM domain

A conserved binding domain that is shared by many proteins (for example, Band4.1, ezrin, radixin, moesin and FAK), which function as linkers between transmembrane proteins and the cytoskeleton. The FERM domain binds to transmembrane proteins and other signalling proteins.

Caveolae

Small invaginations of the plasma membrane (50–100 nm), marked by caveolin-1 protein, that are rich in cholesterol and have a role in signal transduction and endocytosis. Certain cell types, such as endothelial cells, can also contain tubular-vesicular channels of caveolae.

Ascites

Fluid accumulation in the peritoneal cavity, which lines the abdomen.

Pleural fluid

Fluid in the pleural cavity, which surrounds the lungs.

Autophagy

The digestive process by which cells degrade their own components, including damaged organelles.

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Overholtzer, M., Brugge, J. The cell biology of cell-in-cell structures. Nat Rev Mol Cell Biol 9, 796–809 (2008). https://doi.org/10.1038/nrm2504

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