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. 1981 Oct;44(4):506–513. doi: 10.1038/bjc.1981.219

Promotion of fibrosarcoma cell growth by products of syngeneic host macrophages.

G A Currie
PMCID: PMC2010802  PMID: 7295507

Abstract

Cells from a C57BL/cbi chemically induced fibrosarcoma (FS6) require exogenous platelet-derived growth factor (PDGF) for in vitro proliferation (as do normal "untransformed" fibroblasts) whereas cells obtained from the FS6M1 tumour, a spontaneous metastasizing subline, show autonomy from PDGF in vitro. Furthermore, the FS6 cells exhibit very low colony formation in an anchorage-independent growth assay. In vivo, this tumour is immunogenic, rarely metastasizes and is heavily infiltrated by host macrophages. Studies of in vitro cell proliferation and anchorage-independent growth show that syngeneic host macrophages from the peritoneal cavity or from the growing tumour release a diffusible factor(s) which has (1) growth-stimulating activity on FS6 cells in monolayer cultures in PDGF-poor medium and (2) potent colony-stimulating activity on FS6 cell cultured in methyl-cellulose-containing medium. These macrophage supernatants stimulate proliferation of quiescent normal fibroblasts in monolayer culture as well as FS6 sarcoma cells, but do not stimulate anchorage-independent growth of normal cells. Supernatants from BCG-elicited macrophages were shown to contain abundant arginase, and were cytolytic to FS6 cells but not to normal cells. Heat inactivation abrogated the arginase and cytotoxicity, revealing heat-stable mitogenicity for FS6 cells and normal fibroblasts. The stimulatory effect of macrophages on FS6 sarcoma cells can be mimicked by the addition of the tumour promoter 12-tetradecanoyl-phorbol-13-acetate (TPA) and supports the hypothesis that macrophages could play a significant role in multistage carcinogenesis by providing a source of endogenous promoter.

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Selected References

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

  1. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  2. Currie G. A. Activated macrophages kill tumour cells by releasing arginase. Nature. 1978 Jun 29;273(5665):758–759. doi: 10.1038/273758a0. [DOI] [PubMed] [Google Scholar]
  3. Currie G. A., Basham C. Differential arginine dependence and the selective cytotoxic effects of activated macrophages for malignant cells in vitro. Br J Cancer. 1978 Dec;38(6):653–659. doi: 10.1038/bjc.1978.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Currie G. A. Platelet-derived growth-factor requirements for in vitro proliferation of normal and malignant mesenchymal cells. Br J Cancer. 1981 Mar;43(3):335–343. doi: 10.1038/bjc.1981.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DeLustro F., Sherer G. K., LeRoy E. C. Human monocyte stimulation of fibroblast growth by a soluble mediator(s). J Reticuloendothel Soc. 1980 Dec;28(6):519–532. [PubMed] [Google Scholar]
  6. Evans R. Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma. Br J Cancer. 1977 May;35(5):557–566. doi: 10.1038/bjc.1977.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans R. Host cells in transplanted murine tumors and their possible relevance to tumor growth. J Reticuloendothel Soc. 1979 Oct;26(4):427–437. [PubMed] [Google Scholar]
  8. Filkins J. P. Endotoxin-enhanced secretion of macrophage insulin-like activity. J Reticuloendothel Soc. 1980 May;27(5):507–511. [PubMed] [Google Scholar]
  9. Greenburg G. B., Hunt T. K. The proliferative response in vitro of vascular endothelial and smooth muscle cells exposed to wound fluids and macrophages. J Cell Physiol. 1978 Dec;97(3 Pt 1):353–360. doi: 10.1002/jcp.1040970310. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Leibovich S. J., Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol. 1975 Jan;78(1):71–100. [PMC free article] [PubMed] [Google Scholar]
  12. Mantovani A. Effects on in vitro tumor growth of murine macrophages isolated from sarcoma lines differing in immunogenicity and metastasizing capacity. Int J Cancer. 1978 Dec;22(6):741–746. doi: 10.1002/ijc.2910220617. [DOI] [PubMed] [Google Scholar]
  13. Polverini P. J., Cotran P. S., Gimbrone M. A., Jr, Unanue E. R. Activated macrophages induce vascular proliferation. Nature. 1977 Oct 27;269(5631):804–806. doi: 10.1038/269804a0. [DOI] [PubMed] [Google Scholar]
  14. Prehn R. T. Do tumors grow because of the immune response of the host? Transplant Rev. 1976;28:34–42. doi: 10.1111/j.1600-065x.1976.tb00191.x. [DOI] [PubMed] [Google Scholar]
  15. Salmon S. E., Hamburger A. W. Immunoproliferation and cancer: a common macrophage-derived promoter substance. Lancet. 1978 Jun 17;1(8077):1289–1290. doi: 10.1016/s0140-6736(78)91270-9. [DOI] [PubMed] [Google Scholar]
  16. Scher C. D., Pledger W. J., Martin P., Antoniades H., Stiles C. D. Transforming viruses directly reduce the cellular growth requirement for a platelet derived growth factor. J Cell Physiol. 1978 Dec;97(3 Pt 1):371–380. doi: 10.1002/jcp.1040970312. [DOI] [PubMed] [Google Scholar]
  17. Scher C. D., Shepard R. C., Antoniades H. N., Stiles C. D. Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycle. Biochim Biophys Acta. 1979 Aug 10;560(2):217–241. doi: 10.1016/0304-419x(79)90020-9. [DOI] [PubMed] [Google Scholar]

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