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TGFβ in prostate cancer: A growth inhibitor that can enhance tumorigenicity
Author(s) -
Barrack Evelyn R.
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19970401)31:1<61::aid-pros10>3.0.co;2-m
Subject(s) - prostate cancer , autocrine signalling , transforming growth factor , cancer research , cancer , cancer cell , cell growth , prostate , metastasis , in vivo , biology , growth factor , medicine , cell culture , endocrinology , receptor , biochemistry , microbiology and biotechnology , genetics
A common feature of cancer cells is the autocrine production of growth promoters and the loss of function of tumor suppressors. In our search for such features of prostate cancer, we discovered that transforming growth factor β1 (TGFβ1) levels are higher in prostate cancer than in normal prostate, and prostate cancer cells can activate endogenously‐produced latent TGFβ to a bioactive form. Because TGFβ1 is a potent growth inhibitor of epithelial cells, it seems paradoxical that malignant epithelial cells make high levels of a growth inhibitor. Even prostate cancer cells can be growth‐inhibited by TGFβ1, but only under specific conditions in vitro (plating at low cell density in serum‐free medium), and this response is readily disrupted by growth factors, serum, and extracellular matrix, to all of which the cells are exposed in vivo. This explains why prostate cancer cells are resistant to the growth‐inhibitory effect of TGFβ in vivo. In vivo, TGFβ1 actually enhances prostate tumor growth and metastasis, but not by affecting tumor cell proliferation directly. One possibility is that TGFβ affects the host to allow increased numbers of tumor cells to survive and produce progeny. In addition, since prostate cancer cells can still respond to TGFβ, e.g., by increased cell motility, even under conditions that prevent growth inhibition, the ability of TGFβ to enhance tumorigenicity in vivo might also occur via direct effects on the tumor cells themselves. I will discuss new developments in our understanding of TGFβ action, which provide a framework for elucidating the mechanism by which prostate cancer cells have devised a way to protect themselves from being growth‐inhibited by TGFβ1 in vivo. Since the cells retain the ability to be growth‐inhibited by TGFβ, indicating that the TGFβ receptors and signaling pathways for growth inhibition are intact, albeit inactive, it might be possible to reactivate this pathway to achieve a therapeutic benefit in vivo. Prostate 31:61–70, 1997. © 1997 Wiley‐Liss, Inc.