Induction by growth factors from platelets of the focus-forming transformed phenotype in carcinogen-treated C3H/10T1/2 fibroblasts.

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Wounding of mouse skin promotes tumor formation as effectively as 12-O-tetradecanoylphorbol-13-acetate (TPA). Like wounding, TPA stimulates the release of growth factors from platelets and the leakage of plasma from the capillary circulation. Thus, initiated cells in TPA-treated skin are also exposed to the components of whole blood-derived serum. It is possible that serum factors play an important role in the multi-step process of neoplastic transformation. In this study, we evaluate the significance of serum components derived from plasma and platelets in the neoplastic transformation of C3H/10T1/2 mouse fibroblasts exposed to methylcholanthrene. Carcinogen-treated cultures grown to confluence in medium containing 5% whole blood-derived serum (FBS), but maintained for 5 weeks after confluence in plasma-derived serum (PDS), which lacks the platelet components found in whole blood-derived serum, failed to produce transformed foci. The addition of an aqueous extract of platelets to PDS induced the formation of transformed foci with an efficiency comparable to FBS and proportional to the amount and mitogenic activity of the platelet extract. The growth of newly transformed cells was not inhibited by the absence of platelet factors in the culture medium. The loss of density-dependent growth control required at least 3-4 weeks of post-confluence exposure to serum factors derived from platelets. The data suggest that platelet factors induce the conversion of a carcinogen-initiated cell to a focus-forming transformed cell. We demonstrate that platelet-derived growth factor (PDGF) is essential for the induction of the focus-forming phenotype in initiated cells and that PDGF acts co-operatively with the platelet-derived type-beta transforming growth factor and EGF-like growth factor to induce this transformed phenotype. These growth factors may be acting as endogenous promoters of neoplastic transformation of chemically initiated C3H/10T1/2 mouse fibroblasts.