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 TGF alpha-like and TGF beta-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 TGF alpha) and TGF beta. Serum-free medium conditioned by these cells showed differing amounts of TGF alpha-like and TGF beta-like competing activity in EGF and TGF beta radioreceptor assays. Likewise the cells showed differing abilities to bind 125I-labeled EGF and TGF beta. SW 620 cells produced relatively large quantities of TGF alpha-like activity and had no detectable EGF receptors; specific TGF beta binding was observed. SW 480 cells produced the most TGF beta-like activity and had no measurable TGF beta membrane receptors, but EGF receptors were detectable. WIDR cells had both EGF and TGF beta membrane receptors and produced relatively low levels of EGF and TGF beta 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 TGF beta had no significant effect on soft agar growth of the colon carcinoma cells. The production of both TGF alpha-like and TGF beta-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.