Interactions of interferons and transforming growth factors during clonal growth of mouse or human cells in soft agar and in mice.
The mouse fibroblast-like transformed cell line C-243 adapted to growth in suspension was used as a source of virus-induced interferons (MulFN-alpha, beta), and spontaneously produced active growth factors. These factors were purified from C-243 cells grown as tumors in BALB/c mice, and had properties identical to those of TGF-alpha or TGF-beta isolated by others from different tissues. Exogenous TGF-alpha, beta stimulated colony formation by C-243 cells in soft agar, whereas MulFN-alpha, beta inhibited it. Clonal growth of human lung adenocarcinoma A549 cells in soft agar was inhibited as well by human interferons (types alpha, beta, or gamma) as by TGF-beta. Inhibition was dose-related. Pure EGF, which is an analogue of TGF-alpha, diminished the antiproliferative activity of interferons alpha, beta, and gamma in A549 cells. On the other hand, the anti-mitogenic action of IFN-beta and TGF-beta was clearly synergistic. In mice bearing C-243 cell tumors, TGF-alpha, beta stimulated growth, whereas MulFN-alpha, beta inhibited it. Stimulation of tumor growth was also observed after administration of anti-IFN serum that could neutralize endogenous IFN-alpha, beta. The simultaneous administration of MulFN-alpha, beta and TGF-alpha, beta diminished anti-tumor effects of IFN in mice. Our results suggest that both TGFs and IFNs are autocrine, positive or negative growth factors modulating the rate of proliferation and the neoplastic behavior of the cells. The final effects depend on the target-cell sensitivity and on the relative concentration of the various hormone-like factors. Cancer cells overstimulated by TGF-alpha, beta or by EGF may not respond to IFNs.
D000230:Adenocarcinoma / Q000473:pathology; D000362:Agar; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D015291:Transforming Growth Factors
D010455:Peptides; D015291:Transforming Growth Factors; D000362:Agar; D007372:Interferons