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The first evidence of the tumor-induced angiogenesis in vivo by using the chorioallantoic membrane assay dated 1913

Leukemia volume 18, pages 1350–1351 (2004)Cite this article

Virchow, the founder of pathological anatomy, drew attention to the huge number of blood vessels in a tumor mass as long ago as 1865. Tumor vascularization was first studied systematically by Goldman,1 who described the vasoproliferative response of the organ in which a tumor develops as follows: ‘The normal blood vessels of the organs in which the tumor is developing are disturbed by chaotic growth, there is a dilatation and spiralling of the affected vessels, marked capillary budding and new vessel formation, particularly at the advancing border’.

James B Murphy, from the Laboratories of the Rockfeller Institute for Medical Reseach of New York published in 1913 a paper,2 which described, for the first time, the angiogenic response induced by the Jensen rat sarcoma in the chick chorioallantoic membrane (CAM). He wrote that ‘For the general purposes of the experiment it has been found advantageous to use the outer membrane (fused allantois and chorion) for the reason that it lies just under the shell membrane and, therefore, can be inoculated with a minimum amount of trauma. Furthermore, this membrane is the respiratory organ of the chick at this period and is rich in lymphatics and blood vessels. The inoculations were made between the fifth and seventh day of incubation and were allowed to grow until the 18th day. Tumors resulting from such an inoculation of the Jensen sarcoma are found in the membrane as large globular masses lying or suspended from the inner surface of the thin membrane by a broad pedicle.(…) The vessels are much more numerous in the tumors of the embryo, here occurring in two forms, either ingrowths as clusters from the chick membrane or as individual scattered through out the tumor.’

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References

  1. Goldman E . The growth of malignant disease in man and the lower animals with special reference to the vascular system. Lancet 1907; ii: 1236–1240.

    Article  Google Scholar 

  2. Murphy JB . Transplantability of tissues to the embryo of foreign species. Its bearing on questions of tissue specificity and tumor immunity. J Exp Med 1913; 17: 482–493.

    Article  CAS  Google Scholar 

  3. Kunzi-Rapp K, Westphal-Frosch C, Schneckenburger H . Test system for human tumor cell sensitivity to drugs on chicken chorioallantoic membranes. In Vitro Cell Dev Biol 1992; 28A: 565–566.

    Article  CAS  Google Scholar 

  4. Quigley JP, Armstrong PB . Tumor cell intravasation elucidated: the chick embryo opens the window. Cell 1998; 91: 281–284.

    Article  Google Scholar 

  5. Auerbach R, Kubai L, Sidky Y . Angiogenesis induction by tumors, embryonic tissues, and lymphocytes. Cancer Res 1976; 36: 3435–3440.

    CAS  PubMed  Google Scholar 

  6. Leene W, Duyzings MJM, Von Steeg G . Lymphoid stem cell identification in the developing thymus and bursa of Fabricius of the chick. Z Zellforsch 1973; 136: 521–533.

    Article  CAS  Google Scholar 

  7. Solomon JB . Lymphocytopoiesis and ontogeny of defined immunity in birds. In Fetal and Neonatal Immunology, Frontiers of Biology, 1971, Monograph 20, Plenum Press: New York.

  8. Knighton D, Ausprunk D, Tapper D, Folkman J . Avascular and vascular phases of tumor growth in the chick embryo. Br J Cancer 1977; 35: 347–356.

    Article  CAS  Google Scholar 

  9. Ausprunk DH, Knighton DR, Folkman J . Differentiation of the vascular endothelium in the chick chorioallantois: a structural and autoradiographic study. Dev Biol 1974; 38: 237–247.

    Article  CAS  Google Scholar 

  10. Ribatti D, De Falco G, Nico B, Ria R, Crivellato E, Vacca A . In vivo time-course of the angiogenic response induced by multiple myeloma plasma cells in the chick embryo chorioallantoic membrane. J Anat 2003; 203: 323–328.

    Article  Google Scholar 

  11. Ausprunk DH, Knighton DR, Folkman J . Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Am J Pathol 1976; 79: 597–618.

    Google Scholar 

  12. Ausprunk DH, Folkman J . Vascular injury in transplanted tissues. Fine structural changes in tumour, adult, and embryonic blood vessels. Virchows Arch B Cell Pathol 1976; 1: 31–44.

    Google Scholar 

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  1. Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy

    Domenico Ribatti

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Ribatti, D. The first evidence of the tumor-induced angiogenesis in vivo by using the chorioallantoic membrane assay dated 1913. Leukemia 18, 1350–1351 (2004). https://doi.org/10.1038/sj.leu.2403411

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