Colon carcinoma cells switch their response to transforming growth factor beta 1 with tumor progression

Transforming growth factor beta 1 (TGF-beta 1) switches from an inhibitor of tumor cell growth to a stimulator of growth and invasion during human colon carcinoma progression. We originally observed that metastatic colon carcinoma cells in primary culture responded to TGF-beta 1 by proliferation, whereas moderate to well-differentiated primary site colon carcinomas were growth inhibited by TGF-beta 1 (P. Schroy et al., Cancer Res., 50: 261-265, 1990). We then cloned several colon carcinoma cell lines which modeled these responses to TGF-beta 1 and expressed TGF-beta 1 (M. M. Hafez et al., Cell Growth & Differ., 1: 617-626, 1990; 3: 753-762, 1992). Two of these colon carcinoma cell lines, U9 and HD3, which activate approximately equal amounts of TGF-beta 1 and express equal amounts of TGF-beta receptors, are now used to compare the effects of TGF-beta 1 in modulating invasive behavior. The U9 cell line exhibits autocrine-positive growth regulation in vitro by TGF-beta 1, whereas the HD3 cell line shows the opposite response, autocrine-negative regulation. Blocking endogenous TGF-beta 1 with isotype-specific antibody inhibited U9 cell growth because autocrine TGF-beta 1 acts as a mitogen for U9 cells. In contrast, antibody to TGF-beta 1 stimulated HD3 cell proliferation because autocrine TGF-beta 1 inhibits growth of these cells. U9 cells were 13-fold more invasive in vitro through a collagen I layer than HD3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)