Role of Platelet-Derived Tgf?1 in the Progression of Ovarian Cancer.

ABSTRACT: Purpose: Transforming growth factor ?1 (Tgf?1) plays an important role in cancer. Most of Tgf?1 in plasma is from platelets; thus, we studied whether platelet Tgf?1 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 Tgf?1-deficient mice and wild-type mice. Using resected tumor nodules, we studied the effect of platelet Tgf?1 on neoangiogenesis and on platelet extravasation into tumors. To investigate the effect of Tgf?1 at different stages of ovarian cancer, we reduced expression of Tgf?1 receptor (its Tgf?R1 component) in tumors at different time points after injection of cancer cells, and compared the final tumor size.Results: Lack of platelet Tgf?1 in mice reduced tumor growth, neoangiogenesis, and platelet extravasation. Ovarian cancer tumors in platelet-specific Tgf?1-deficient mice reached less than half of their size in wild-type littermates. Knockdown of Tgf?R1 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 Tgf?1 increased the growth of primary tumors in murine models of ovarian cancer. We also showed that inhibition of Tgf?R1 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 Tgf?1 in ovarian cancer. Clin Cancer Res; 23(18); 5611-21. ©2017 AACR.

SUBMITTER: Hu Q 

PROVIDER: S-EPMC5600833 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature