Role of Platelet-Derived Tgfβ1 in the Progression of Ovarian Cancer
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....
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| Vydáno v: | Clinical cancer research Ročník 23; číslo 18; s. 5611 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
15.09.2017
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| ISSN: | 1078-0432, 1557-3265, 1557-3265 |
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| Abstract | 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.
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.
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.
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.
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| AbstractList | 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.
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.
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.
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.
. 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.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 | Wong, Stephen T C Cho, Min Soon Pradeep, Sunila Afshar-Kharghan, Vahid Haemmerle, Monika Rodriguez-Aguayo, Cristian Hu, Qianghua Lopez-Berestein, Gabriel Sood, Anil K Rupaimoole, Rajesha Hisamatsu, Takeshi |
| Author_xml | – sequence: 1 givenname: Qianghua surname: Hu fullname: Hu, Qianghua organization: Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 2 givenname: Takeshi surname: Hisamatsu fullname: Hisamatsu, Takeshi organization: Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 3 givenname: Monika surname: Haemmerle fullname: Haemmerle, Monika organization: Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 4 givenname: Min Soon surname: Cho fullname: Cho, Min Soon organization: Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 5 givenname: Sunila surname: Pradeep fullname: Pradeep, Sunila organization: Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 6 givenname: Rajesha surname: Rupaimoole fullname: Rupaimoole, Rajesha organization: Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 7 givenname: Cristian surname: Rodriguez-Aguayo fullname: Rodriguez-Aguayo, Cristian organization: Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 8 givenname: Gabriel surname: Lopez-Berestein fullname: Lopez-Berestein, Gabriel organization: Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 9 givenname: Stephen T C surname: Wong fullname: Wong, Stephen T C organization: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, Texas – sequence: 10 givenname: Anil K surname: Sood fullname: Sood, Anil K email: vakharghan@mdanderson.org, asood@mdanderson.org organization: Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. vakharghan@mdanderson.org asood@mdanderson.org – sequence: 11 givenname: Vahid surname: Afshar-Kharghan fullname: Afshar-Kharghan, Vahid email: vakharghan@mdanderson.org, asood@mdanderson.org organization: Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas. vakharghan@mdanderson.org asood@mdanderson.org |
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| Snippet | 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... 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... |
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| SubjectTerms | Animals Blood Platelets - metabolism Cell Line, Tumor Cell Proliferation Disease Models, Animal Disease Progression Female Gene Expression Heterografts Humans Immunohistochemistry Mice Mice, Transgenic Neovascularization, Pathologic - genetics Neovascularization, Pathologic - metabolism Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology RNA, Small Interfering - genetics Time Factors Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - metabolism Tumor Burden |
| Title | Role of Platelet-Derived Tgfβ1 in the Progression of Ovarian Cancer |
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