Role of platelet-derived Tgfβ1 in the progression of ovarian cancer

Purpose: Transforming growth factor b1 (Tgfb1) plays an important role in cancer. Most of Tgfb1 in plasma is from platelets; thus, we studied whether platelet Tgfb1 has any role in the progression of ovarian cancer, and whether this role is limited to metastasis or also involves the growth of primary tumors. Experimental Design: We compared the growth of murine ovarian cancer cell-induced tumors in platelet-specific Tgfb1-deficient mice and wild-type mice. Using resected tumor nodules, we studied the effect of platelet Tgfb1 on neoangiogenesis and on platelet extravasation into tumors. To investigate the effect of Tgfb1 at different stages of ovarian cancer, we reduced expression of Tgfb1 receptor (its TgfbR1 component) in tumors at different time points after injection of cancer cells, and compared the final tumor size. Results: Lack of platelet Tgfb1 in mice reduced tumor growth, neoangiogenesis, and platelet extravasation. Ovarian cancer tumors in platelet-specific Tgfb1-deficient mice reached less than half of their size in wild-type littermates. Knockdown of TgfbR1 on cancer cells in the first 2 weeks after their injection reduced tumor growth, but was less effective if initiated after 3 weeks. Conclusions: We showed that platelet Tgfb1 increased the growth of primary tumors in murine models of ovarian cancer. We also showed that inhibition of TgfbR1 is more effective in reducing the growth of ovarian cancer if initiated earlier. Our results supported a therapeutic benefit in preventing platelet activation, degranulation, and release of Tgfb1 in ovarian cancer.