Transforming growth factor-beta inhibits proliferation of human ovarian cancer cells obtained from ascites.
BACKGROUND: Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor-beta and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth-inhibited by or produce transforming growth factor-beta. METHODS: Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti-CD45 antibody. The effect of transforming growth factor-beta on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor-beta 1 and beta 2 also was performed in these cells. RESULTS: Transforming growth factor-beta (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28% of control values. In addition, there was no difference in dose-dependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61%) were found to express immunohistochemically detectable transforming growth factor-beta, but immunostaining was not observed in 39% of cases. CONCLUSIONS: Although most primary ovarian cancer cells remain sensitive to the growth-inhibitory effect of transforming growth factor-beta, loss of production may interrupt the transforming growth factor-beta autocrine inhibitory loop and play a role in the development of some ovarian cancers.
Hurteau, J; Rodriguez, GC; Whitaker, RS; Shah, S; Mills, G; Bast, RC; Berchuck, A
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