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

Abstract
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)
AuthorsS Hsu, F Huang, M Hafez, S Winawer, E Friedman
JournalCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research (Cell Growth Differ) Vol. 5 Issue 3 Pg. 267-75 (Mar 1994) ISSN: 1044-9523 [Print] United States
PMID8018559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Proto-Oncogene Proteins c-fos
  • Transforming Growth Factor beta
  • Collagen
Topics
  • Animals
  • Cell Division (physiology)
  • Collagen
  • Colonic Neoplasms (pathology)
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-fos (biosynthesis)
  • Transforming Growth Factor beta (physiology)
  • Tumor Cells, Cultured

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