Production of Transforming Growth Factors by Human Colon Cancer Lines

Abstract

Three human colon cancer lines (SW 480, SW 620, WIDR) were characterized as to their production of molecules with transforming growth factor (TGF)-like activity. Production of both TGFα-like and TGFβ-like activity was quantitated, as were cellular receptors for these molecules, and growth response in soft agar to exogenous epidermal growth factor (EGF) (as a substitute for TGFα) and TGFβ. Serum-free medium conditioned by these cells showed differing amounts of TGFα-like and TGFβ-like competing activity in EGF and TGFβ radioreceptor assays. Likewise the cells showed differing abilities to bind ¹²⁵I-labeled EGF and TGFβ. SW 620 cells produced relatively large quantities of TGFα-like activity and had no detectable EGF receptors; specific TGFβ binding was observed. SW 480 cells produced the most TGFβ-like activity and had no measurable TGFβ membrane receptors, but EGF receptors were detectable. WIDR cells had both EGF and TGFβ membrane receptors and produced relatively low levels of EGF and TGFβ receptor-competing activity. All three of the cell lines grew spontaneously in soft agar (in medium containing 10% serum). In contrast to other carcinoma cell lines, exogenous EGF and TGFβ had no significant effect on soft agar growth of the colon carcinoma cells. The production of both TGFα-like and TGFβ-like polypeptides by colon carcinoma cell lines has been shown, yet involvement of these factors in autostimulatory activity could not be demonstrated. The possibility that these endogenous factors could be involved in paracrine stimulation of stromal cells remains to be explored.