Summary
Immunohistochemical, cytochemical and ultrastructural data showing vivid angiogenesis and numerous mast cells (MCs) in the bone marrow of 24 patients with active multiple myeloma (MM) compared with 34 patients with non-active MM and 22 patients with monoclonal gammopathy of undetermined significance (MGUS) led us to hypothesize that angiogenesis parallels progression of MM, and that MCs participate in its induction via angiogenic factors in their secretory granules.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Alessandri, G., Raju, K. S. & Gullino, P. M. (1984). Characterization of a chemoattractant from endothelium induced by angiogenic effectors. Cancer Res 44: 1579–1584.
Aznavoorian, S., Murphy, A. N., Stetler-Stevenson, W. G. & Liotta, L. A. (1993). Molecular aspects of tumor cell invasion and metastasis. Cancer 71: 1368–1383.
Beil, W. J., Login, G. R., Galli, S. J. & Dvorak, A. M. (1994). Ultrastructural immunogold localization of tumor necrosis factor-α on the cytoplasmic granules of rat peritoneal mast cells with rapid microwave fixation. J Allergy Clin Immunol 94: 531–536.
Blair, R. J., Mengh, H., Marchese, M. J., Ren, S., Schwartz, L. B., Tonnesen, M. G. & Gruber, B. L. (1997). Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Invest 99: 2691–2700.
Bussolino, F., Ziche, M., Wang, J. M., Alessi, D., Morbidelli, L., Cremona, O., Bosia, A., Marchisio, P. C. & Mantovani, A. (1991). In vitro and in vivo activation of endothelial cells by colony stimulating factors. J Clin Invest 87: 986–995.
Castellot, J. J., Karnovsky, M. J. & Spiegelman, B. M. (1982). Differentiation-dependent stimulation of neovascularization and endothelial cell chemotaxis by 3T3 adipocytes. Proc Natl Acad Sci USA 79: 5597–5601.
Cozzolino, F., Torcia, M., Aldinucci, D., Rubatelli, A., Miliani, A., Shaw, A. R., Lansdorp, P. M. & Di Guglielmo, R. (1989). Production of interleukin-1 by bone marrow myeloma cells. Blood 74: 380–387.
Dethlefsen, S. M., Matsuura, N. & Zetter, B. R. (1994). Mast cell accumulation at sites of murine tumor implantation: implications for angiogenesis and tumor metastasis. Invasion Metastasis 14: 395–408.
Durie, B. G. M. (1991). Staging and kinetics of multiple myeloma. In Neoplastic Disorders of the Blood, Wiernik PH, Canellos GP, Kyle RA, Schiffer CA (eds.), pp. 439–451, Churchill Livingstone: New York
Durie, B. G. M. & Salmon, S. E. (1977). Multiple myeloma, macroglobulinemia and monoclonal gammapathies. In Recent Advances in Haematology, Hoggbrand AV, Blain MC, Hirsh H (eds), pp. 243–261, Churchill Livingstone: New York
Elias, H. & Hyde, D. M. (1983). Stereological measurements of isotropic structures. In A Guide to Practical Stereology, Elias H, Hyde DM (eds.), pp. 25–44, Karger: Basel
Folkman, J. (1995). Clinical applications of research on angiogenesis. N Engl J Med 333: 1757–1763.
Gruber, B. L., Marchese, M. J. & Kew, R. (1995). Angiogenic factors stimulate mast cell migration. Blood 86: 2488–2493.
Grutzkan, A., Kruger-Krasagakes, S., Kogel, H., Schwarz, C., Henz, B. M. & Moller, A. (1996). Synthesis, storage and release of the vascular endothelial growth factor by human mast cells. Mol Biol Cell 7: 352A
Hamada, J., Cavanangh, P. G. & Lotan, O. (1992). Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. Br J Cancer 66: 349–354.
Hanahan, D. & Folkman, J. (1996). Pattern and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 66: 353–364.
Jakobson, A. M. & Hahnenberger, R. (1991). Antiangiogenic effect of heparin and other sulphated glycosaminoglycans in the chick embryo chorioallantoic membrane. Pharmacol Toxicol 69: 122–126.
Kessler, D. A., Langer, R. S., Pless, N. A. & Folkman, J. (1976). Mast cells and tumor angiogenesis. Int J Cancer 18: 703–709.
Klein, B. (1995). Cytokine, cytokine receptors, transduction signals and oncogenes in human multiple myeloma. Semin Hematol 32: 4–19.
Kops, S. K., Van Loveren, H., Rosenstein, R. W., Ptak, W. & Askenase, P. W. (1984). Mast cell activation and vascular alterations in immediate hypersensitivity-like reactions induced by a T-cell-derived antigen-binding factor. Lab Invest 50: 421–434.
Lichtenstein, A., Berenson, J., Norman, D., Chang, M-P & Carlile, A. (1989). Production of cytokines by bone marrow cells obtained from patients with multiple myeloma. Blood 74: 1266–1273.
Meininger, E. J. & Zetter, B. R. (1992). Mast cells and angiogenesis. Semin Cancer Biol 3: 73–79.
Mignatti, P. & Rifkin, D. B. (1993). Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73: 161–195.
Motro, B., Itin, A., Sachs, L. & Keshet, E. (1990). Pattern of interleukin 6 gene expression in vivo suggests a role for this cytokine in angiogenesis. Proc Natl Acad Sci USA 87: 4068–4072.
Nakamura, M., Merchav, S., Carter, A., Ernst, T. J., Demetri, G. D., Furukawa, Y., Anderson, K., Freedman, A. S. & Griffin, J. D. (1989). Expression of a novel 3.5-kb macrophage colony-stimulating factor transcript in human myeloma cells. J Immunol 143: 3543–3547.
Norrby, K. (1993). Heparin and angiogenesis: a low molecular weight fraction inhibits and a high-molecular weight fraction stimulates angiogenesis systematically. Haemostasis 23: (suppl. 1) 144–149.
Norrby, K. (1996). Interleukin-8 and de novo mammalian angiogenesis. Cell Proliferation 29: 315–323.
Norrby, K. & Whooley, D. (1993). Role of mast cells in mitogenesis and angiogenesis in normal tissues and tumour tissues. Adv Biosci 89: 71–136.
Polverini, P. F. (1996). How the extracellular matrix and macrophages contribute to angiogenesis-dependent diseases. Eur J Cancer 32A: 2430–2437.
Poole, T. J. & Zetter, B. R. (1983). Mast cell chemotaxis to tumor derived factors. Cancer Res 43: 5857–5862.
Qu, Z., Leibler, J. M., Powers, M. R., Galey, T., Ahmadi, P., Huang, X. N., Ansel, J. C., Butterfield, J. H., Planck, S. R. & Rosenbaum, J. T. (1995). Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangiomas. Am J Pathol 147: 564–573.
Ribatti, D., Roncali, L., Nico, B. & Bertossi, M. (1987). Effects of exogenous heparin on the vasculogenesis of the chorioallantoic membrane. Acta Anat 130: 257–263.
Ribatti, D., Contino, R. & Tursi, A. (1988). Do mast cells intervene in the vasoproliferative processes of the rheumatoid synovitis?. J Submicrosc Cytol Pathol 20: 635–637.
Ribatti, D., Nico, B., Vacca, A., Marzullo, A., Calvi, N., Roncali, L. & Dammacco, F. (1998). Do mast cells help to induce angiogenesis in B-cell non-Hodgkin lymphomas?. Br J Cancer 77: 1900–1906.
Roberts, A. B., Sporn, M. B., Assoian, R. K., Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, V. I., Liotta, L. A., Falanga, V., Kehr, J. H. & Fauci, A. S. (1986). Transforming growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83: 4167–4171.
Schwab, G., Siegall, C. B., Aarden, L. A., Neckers, L. M. & Nordan, R. P. (1991). Characterization of an interleukin-6 mediated autocrine growth loop in the human multiple myeloma cell line, U266. Blood 77: 587
Sorbo, J., Jakobson, A. & Norrby, K. (1994). Mast cell histamine is angiogenic through receptors for histamine 1 and histamine 2. Int J Exp Pathol 75: 43–50.
Starkey, J. R., Crowle, P. K. & Taubenberger, S. (1988). Mast cell-deficient W/Wv mice exhibit a decreased rate of tumor angiogenesis. Int J Cancer 42: 48–52.
Taylor, S. & Folkman, J. (1982). Protamine is an inhibitor of angiogenesis. Nature 297: 307–312.
Thorton, S. C., Mueller, S. M. & Levine, E. M. (1983). Human endothelial cells: use of heparin in cloning and long term cultivation. Science 222: 623–625.
Vacca, A., Ribatti, D., Roncali, L., Ranieri, G., Serio, G., Silvestris, F. & Dammacco, F. (1994). Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 87: 503–508.
Vacca, A., Moretti, S., Ribatti, D., Pellegrino, A., Pimpinelli, N., Bianchi, B., Bonifazi, E., Ria, R., Serio, G. & Dammacco, F. (1997). Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9. Eur J Cancer 33: 1685–1692.
Wilks, J. M., Scott, P. S., Urla, L. K. & Cocuzza, J. M. (1991). Inhibition of angiogenesis with combination treatments of angiostatic steroids and suramin. Int J Radiat Biol 60: 73–77.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Ribatti, D., Vacca, A., Nico, B. et al. Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma. Br J Cancer 79, 451–455 (1999). https://doi.org/10.1038/sj.bjc.6690070
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690070
Keywords
This article is cited by
-
Emerging roles for myeloid immune cells in bone metastasis
Cancer and Metastasis Reviews (2021)
-
VEGFA and VEGFR2 RNAscope determination in gastric cancer
Journal of Molecular Histology (2018)
-
Rhu-Epo down-regulates pro-tumorigenic activity of cancer-associated fibroblasts in multiple myeloma
Annals of Hematology (2018)
-
Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma
Clinical and Experimental Medicine (2017)
-
Spatial distribution of mast cells around vessels and glands in human gastric carcinoma
Clinical and Experimental Medicine (2017)