Promotion of fibrosarcoma cell growth by products of syngeneic host macrophages.
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.
D000818:Animals; D001119:Arginase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D005354:Fibrosarcoma / Q000473:pathology*; D006133:Growth Substances / Q000378:metabolism*; D006358:Hot Temperature; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor; D012513:Sarcoma, Experimental / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006133:Growth Substances; D008934:Mitogens; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D001119:Arginase; D013755:Tetradecanoylphorbol Acetate