論文 - 詳細
| RRC ID | 43968 |
|---|---|
| 著者 | Takahashi Y, Koyanagi T, Suzuki Y, Saga Y, Kanomata N, Moriya T, Suzuki M, Sato Y. |
| タイトル | Vasohibin-2 expressed in human serous ovarian adenocarcinoma accelerates tumor growth by promoting angiogenesis. |
| ジャーナル | Mol Cancer Res |
| Abstract |
Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor and VASH2 is its homolog. Our previous analysis revealed that VASH1 is expressed in endothelial cells to terminate angiogenesis, whereas VASH2 is expressed in infiltrating mononuclear cells mobilized from bone marrow to promote angiogenesis in a mouse model of hypoxia-induced subcutaneous angiogenesis. To test the possible involvement of VASH2 in the tumor, we examined human ovarian cancer cells for the presence of VASH2. Immunohistochemical analysis revealed that VASH2 protein was preferentially detected in cancer cells of serous ovarian adenocarcinoma. We then used SKOV-3 and DISS, two representative human serous adenocarcinoma cell lines, and examined the role of VASH2 in the tumor. The knockdown of VASH2 showed little effect on the proliferation of cancer cells in vitro but notably inhibited tumor growth, peritoneal dissemination, and tumor angiogenesis in a murine xenograft model. Next, we stably transfected the human VASH2 gene into two types of murine tumor cells, EL-4 and MLTC-1, in which endogenous VASH2 was absent. When either EL-4 or MLTC-1 cells were inoculated into VASH2 (-/-) mice, the VASH2 transfectants formed bigger tumors when compared with the controls, and the tumor microvessel density was significantly increased. VASH2 stimulated the migration of endothelial cells, and its increased expression in cancer cells is related to the decrease of mir-200b. These results indicate that VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. |
| 巻・号 | 10(9) |
| ページ | 1135-46 |
| 公開日 | 2012-9-1 |
| DOI | 10.1158/1541-7786.MCR-12-0098-T |
| PII | 1541-7786.MCR-12-0098-T |
| PMID | 22826464 |
| MeSH | Angiogenic Proteins / genetics* Angiogenic Proteins / metabolism Animals Cell Line, Tumor Cell Migration Assays Cell Proliferation Cystadenocarcinoma, Serous / blood supply Cystadenocarcinoma, Serous / genetics* Cystadenocarcinoma, Serous / metabolism Cystadenocarcinoma, Serous / secondary DNA, Complementary / genetics Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Human Umbilical Vein Endothelial Cells Humans Immunohistochemistry Kaplan-Meier Estimate Mice Mice, Inbred BALB C Mice, Nude Neovascularization, Pathologic / metabolism* Ovarian Neoplasms / blood supply Ovarian Neoplasms / genetics* Ovarian Neoplasms / metabolism Ovarian Neoplasms / pathology Peritoneal Neoplasms / blood supply Peritoneal Neoplasms / genetics Peritoneal Neoplasms / metabolism Peritoneal Neoplasms / secondary* Xenograft Model Antitumor Assays |
| IF | 4.63 |
| 引用数 | 46 |
| WOS 分野 | ONCOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OV2944-HM-1(RCB1483) |