Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Apr;119(1):57–64.

Mast cells and tumors. The specific enhancement of tumor proliferation in vitro.

W R Roche
PMCID: PMC1888089  PMID: 3985123

Abstract

Mast cells were found to be unique among the peritoneal leukocytes by virtue of their capacity to enhance profoundly the proliferation of a variety of tumors in vitro. This phenomenon occurs at mast cell/tumor ratios which reflect the stoichiometry of host cell/tumor relationships in vivo. The growth factor was found to reside in mast cell granules and was identified as heparin by sequential purification and enzymatic degradation. This cellular interaction was tumor-specific, although isolated granules could enhance fibroblast proliferation. The findings are discussed in relation to previous morphologic studies, reports of in vitro mast-cell-mediated tumor cytotoxicity, and the role of mast cells in angiogenesis and connective tissue proliferation.

Full text

PDF
59

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkins F. M., Metcalfe D. D. Degradation of the heparin matrix of mast cell granules by cultured fibroblasts. J Immunol. 1983 Sep;131(3):1420–1425. [PubMed] [Google Scholar]
  2. Azizkhan R. G., Azizkhan J. C., Zetter B. R., Folkman J. Mast cell heparin stimulates migration of capillary endothelial cells in vitro. J Exp Med. 1980 Oct 1;152(4):931–944. doi: 10.1084/jem.152.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CSABA G., ACS T., HORVATH C., MOLD K. Genesis and function of mast cells. Mast cell and plasmacyte reaction to induced, homologous and heterologous tumours. Br J Cancer. 1961 Jun;15:327–335. doi: 10.1038/bjc.1961.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dvorak A. M., Galli S. J., Galli A. S., Hammond M. E., Churchill W. H., Jr, Dvorak H. F. Tumor-basophil interactions in vitro--a scanning and transmission electron microscopic study. J Immunol. 1979 Jun;122(6):2447–2457. [PubMed] [Google Scholar]
  5. Farram E., Nelson D. S. Mouse mast cells as anti-tumor effector cells. Cell Immunol. 1980 Oct;55(2):294–301. doi: 10.1016/0008-8749(80)90162-8. [DOI] [PubMed] [Google Scholar]
  6. Franzén, Norrby K. Local mitogenic effect of tissue mast cell secretion. Cell Tissue Kinet. 1980 Nov;13(6):635–642. doi: 10.1111/j.1365-2184.1980.tb00502.x. [DOI] [PubMed] [Google Scholar]
  7. Frieri M., Metcalfe D. D. Analysis of the effect of mast cell granules on lymphocyte blastogenesis in the absence and presence of mitogens: identification of heparin as a granule-associated suppressor factor. J Immunol. 1983 Oct;131(4):1942–1948. [PubMed] [Google Scholar]
  8. Hartveit F., Halleraker B. Changes in the connective tissue and inflammatory response to Ehrlich's carcinoma following treatment of the host mice with butazolidine. Acta Pathol Microbiol Scand A. 1970;78(5):516–524. doi: 10.1111/j.1699-0463.1970.tb02534.x. [DOI] [PubMed] [Google Scholar]
  9. Hartveit F. Mast cells and metachromasia in human breast cancer: their occurrence, significance and consequence: a preliminary report. J Pathol. 1981 May;134(1):7–11. doi: 10.1002/path.1711340103. [DOI] [PubMed] [Google Scholar]
  10. Hartveit F., Sandstad E. Stromal metachromasia: a marker for areas of infiltrating tumour growth? Histopathology. 1982 Jul;6(4):423–428. doi: 10.1111/j.1365-2559.1982.tb02739.x. [DOI] [PubMed] [Google Scholar]
  11. Henderson W. R., Chi E. Y., Jong E. C., Klebanoff S. J. Mast cell-mediated tumor-cell cytotoxicity. Role of the peroxidase system. J Exp Med. 1981 Mar 1;153(3):520–533. doi: 10.1084/jem.153.3.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hewitt H. B., Blake E. R., Walder A. S. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br J Cancer. 1976 Mar;33(3):241–259. doi: 10.1038/bjc.1976.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. JAQUES L. B., MONKHOUSE F. C., STEWART M. A method for the determination of heparin in blood. J Physiol. 1949 Aug;109(1-2):41–48. doi: 10.1113/jphysiol.1949.sp004367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jaques L. B. Heparins--anionic polyelectrolyte drugs. Pharmacol Rev. 1979 Jun;31(2):99–166. [PubMed] [Google Scholar]
  15. Kaliner M. A. The mast cell--a fascinating riddle. N Engl J Med. 1979 Aug 30;301(9):498–499. doi: 10.1056/NEJM197908303010910. [DOI] [PubMed] [Google Scholar]
  16. Krüger P. G., Lagunoff D. Effect of age on mast cell granules. Int Arch Allergy Appl Immunol. 1981;65(3):291–299. doi: 10.1159/000232768. [DOI] [PubMed] [Google Scholar]
  17. LAGUNOFF D., BENDITT E. P. Proteolytic enzymes of mast cells. Ann N Y Acad Sci. 1963 Feb 26;103:185–198. doi: 10.1111/j.1749-6632.1963.tb53698.x. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Leibovich S. J., Ross R. A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol. 1976 Sep;84(3):501–514. [PMC free article] [PubMed] [Google Scholar]
  20. Lippman M. M., Mathews M. B. Heparins: varying effects on cell proliferation in vitro and lack of correlation with anticoagulant activity. Fed Proc. 1977 Jan;36(1):55–59. [PubMed] [Google Scholar]
  21. Martin B. M., Gimbrone M. A., Jr, Unanue E. R., Cotran R. S. Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor. J Immunol. 1981 Apr;126(4):1510–1515. [PubMed] [Google Scholar]
  22. Nelson M., Nelson D. S., Hopper K. E. I. Tumor growth in mice with depressed capacity to mount inflammatory responses: possible role of macrophages. Am J Pathol. 1981 Aug;104(2):114–124. [PMC free article] [PubMed] [Google Scholar]
  23. Nelson M., Nelson D. S. II. Tumor growth at sites of inflammation induced by mitogens in mice. Am J Pathol. 1981 Aug;104(2):125–131. [PMC free article] [PubMed] [Google Scholar]
  24. Piepkorn M. W., Daynes R. A. Heparin effect on DNA synthesis in a murine fibrosarcoma cell line: influence of anionic density. J Natl Cancer Inst. 1983 Sep;71(3):615–618. [PubMed] [Google Scholar]
  25. Prehn R. T. The immune reaction as a stimulator of tumor growth. Science. 1972 Apr 14;176(4031):170–171. doi: 10.1126/science.176.4031.170. [DOI] [PubMed] [Google Scholar]
  26. Rudland P. S., Jimenez de Asua L. Action of growth factors in the cell cycle. Biochim Biophys Acta. 1979 Feb 4;560(1):91–133. doi: 10.1016/0304-419x(79)90004-0. [DOI] [PubMed] [Google Scholar]
  27. Sterk A. R., Ishizaka T. Binding properties of IgE receptors on normal mouse mast cells. J Immunol. 1982 Feb;128(2):838–843. [PubMed] [Google Scholar]
  28. Subba Rao P. V., Friedman M. M., Atkins F. M., Metcalfe D. D. Phagocytosis of mast cell granules by cultured fibroblasts. J Immunol. 1983 Jan;130(1):341–349. [PubMed] [Google Scholar]
  29. Thornton S. C., Mueller S. N., Levine E. M. Human endothelial cells: use of heparin in cloning and long-term serial cultivation. Science. 1983 Nov 11;222(4624):623–625. doi: 10.1126/science.6635659. [DOI] [PubMed] [Google Scholar]
  30. Timonen T., Reynolds C. W., Ortaldo J. R., Herberman R. B. Isolation of human and rat natural killer cells. J Immunol Methods. 1982;51(3):269–277. doi: 10.1016/0022-1759(82)90393-3. [DOI] [PubMed] [Google Scholar]
  31. Uvnäs B. Histamine storage and release. Fed Proc. 1974 Oct;33(10):2172–2176. [PubMed] [Google Scholar]
  32. Vadas M. A., David J. R., Butterworth A., Pisani N. T., Siongok T. A. A new method for the purification of human eosinophils and neutrophils, and a comparison of the ability of these cells to damage schistosomula of Schistosoma mansoni. J Immunol. 1979 Apr;122(4):1228–1236. [PubMed] [Google Scholar]
  33. Wiebkin O. W., Muir H. Synthesis of proteoglycans by suspension and monolayer cultures of adult chondrocytes and de novo cartilage nodules-the effect of hyaluronic acid. J Cell Sci. 1977;27:199–211. doi: 10.1242/jcs.27.1.199. [DOI] [PubMed] [Google Scholar]
  34. Yamagata T., Saito H., Habuchi O., Suzuki S. Purification and properties of bacterial chondroitinases and chondrosulfatases. J Biol Chem. 1968 Apr 10;243(7):1523–1535. [PubMed] [Google Scholar]
  35. Yang T. K., Jenkin H. M. The effect of heparin on growth of mammalian cells in vitro. Proc Soc Exp Biol Med. 1978 Oct;159(1):88–93. doi: 10.3181/00379727-159-40290. [DOI] [PubMed] [Google Scholar]
  36. Yurt R. W., Leid R. W., Jr, Austen K. F. Native heparin from rat peritoneal mast cells. J Biol Chem. 1977 Jan 25;252(2):518–521. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES