Role of Platelet-Derived Tgfβ1 in the Progression of Ovarian Cancer. Clin Cancer Res 2017 Sep 15;23(18):5611-5621
Date
06/15/2017Pubmed ID
28611202Pubmed Central ID
PMC5600833DOI
10.1158/1078-0432.CCR-16-3272Scopus ID
2-s2.0-85029472021 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
Purpose: Transforming growth factor β1 (Tgfβ1) plays an important role in cancer. Most of Tgfβ1 in plasma is from platelets; thus, we studied whether platelet Tgfβ1 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 Tgfβ1-deficient mice and wild-type mice. Using resected tumor nodules, we studied the effect of platelet Tgfβ1 on neoangiogenesis and on platelet extravasation into tumors. To investigate the effect of Tgfβ1 at different stages of ovarian cancer, we reduced expression of Tgfβ1 receptor (its TgfβR1 component) in tumors at different time points after injection of cancer cells, and compared the final tumor size.Results: Lack of platelet Tgfβ1 in mice reduced tumor growth, neoangiogenesis, and platelet extravasation. Ovarian cancer tumors in platelet-specific Tgfβ1-deficient mice reached less than half of their size in wild-type littermates. Knockdown of TgfβR1 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 Tgfβ1 increased the growth of primary tumors in murine models of ovarian cancer. We also showed that inhibition of TgfβR1 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 Tgfβ1 in ovarian cancer. Clin Cancer Res; 23(18); 5611-21. ©2017 AACR.
Author List
Hu Q, Hisamatsu T, Haemmerle M, Cho MS, Pradeep S, Rupaimoole R, Rodriguez-Aguayo C, Lopez-Berestein G, Wong STC, Sood AK, Afshar-Kharghan VAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Platelets
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Disease Progression
Female
Gene Expression
Heterografts
Humans
Immunohistochemistry
Mice
Mice, Transgenic
Neovascularization, Pathologic
Ovarian Neoplasms
RNA, Small Interfering
Time Factors
Transforming Growth Factor beta1
Tumor Burden
