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)