TRANSFORMING GROWTH-FACTOR-BETA INHIBITS PROLIFERATION OF HUMAN OVARIAN-CANCER CELLS OBTAINED FROM ASCITES

Background. Previously, the authors found that immortalized ovarian ca ncer cell lines generally were resistant to the growth inhibitory effe ct of transforming growth factor-beta and frequently had lost the abil ity to produce or activate this growth factor. In this study, the auth ors examined whether early passage epithelial ovarian cancer cells obt ained from ascites are growth-inhibited by or produce transforming gro wth factor-beta. Methods. Ovarian cancer cells were purified from asci tes by percoll gradient density centrifugation, and inflammatory cells were removed using anti-CD45 antibody. The effect of transforming gro wth factor-beta on the proliferation of ovarian cancer cells was asses sed using the thymidine incorporation assay. Immunohistochemical stain ing for transforming growth factor-beta 1 and beta 2 also was performe d in these cells. Results. Transforming growth factor-beta (10 ng/ml) significantly inhibited [H-3]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inh ibition was seen, the mean thymidine incorporation was 33 plus or minu s 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%) w ere found to express immunohistochemically detectable transforming gro wth factor-beta, but immunostaining was not observed in 39% of cases. Conclusions. Although most primary ovarian cancer cells remain sensiti ve 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 o varian cancers.