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Induction of Carcinoembryonic Antigen Secretion and Modulation of Protein Secretion/Expression and Fibronectin/Laminin Expression in Human Colon Carcinoma Cells by Transforming Growth Factor-ß¹

Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 [S. C., A. T., M. G. B.], and the Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109 [J. V.]

We have recently reported that TGF-ß induces a response similar to that of planar polar differentiation promoters in human colon carcinoma MOSER cells. N,N-Dimethylformamide and TGF-ß had similar effects on MOSER cells with respect to reversible inhibition of growth (both in monolayer culture and semisolid medium), induction of fibronectin expression and the induction of morphological alterations (Cancer Res., 47: 2950–2954, 1987). Since the expression of carcinoembryonic antigen (CEA) has been reported to be modulated by planar polar compounds that promote differentiation in colon carcinomas, we addressed the issue of whether the differentiation-like effects of TGF-ß on these cells would also encompass modulation of CEA expression in the MOSER cells. The biological modulating effects of TGF-ß on extracellular matrix glycoprotein expression and the expression and secretion of cellular proteins were also studied in view of the reported modulating effects of this growth factor on untransformed, noncolonic cells. In this communication we report that TGF-ß induced the synthesis of fibronectin and laminin but not collagen IV. TGF-ß also induced CEA secretion in a dose-dependent manner. Elevated CEA secretion was detected following 48 h of TGF-ß treatment and a 16-fold increase in CEA secretion was observed following 7 days of treatment. The cells were committed to secrete CEA following one dose of TGF-ß treatment.

The enhanced expression of four cellular proteins (M_r 42,000, M_r 48,000, M_r 52,000, and M_r 55,000) and the enhanced secretion of three proteins (M_r 66,000, M_r 200,000, and M_r 400,000) were also induced. Some of these protein alterations were detected as early as 6–24 h following TGF-ß treatment. It is concluded that TGF-ß modulated the production and secretion of CEA, the synthesis of fibronectin and laminin, and the expression and secretion of several cellular proteins in the colon carcinoma MOSER cells. To our knowledge, this is the first report on the modulation of CEA and laminin by TGF-ß in tissue-cultured cells, and is the first report on the modulation of cellular proteins by this growth factor in human colon carcinoma cells.

¹ Supported by NIH Grant CA34432.

² To whom requests for reprints should be addressed, at Bristol-Baylor Laboratory, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

Received 1/ 4/88. Accepted 4/12/88.

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