論文 - 詳細
| RRC ID | 72339 |
|---|---|
| 著者 | Odagiri H, Kadomatsu T, Endo M, Masuda T, Morioka MS, Fukuhara S, Miyamoto T, Kobayashi E, Miyata K, Aoi J, Horiguchi H, Nishimura N, Terada K, Yakushiji T, Manabe I, Mochizuki N, Mizuta H, Oike Y. |
| タイトル | The secreted protein ANGPTL2 promotes metastasis of osteosarcoma cells through integrin α5β1, p38 MAPK, and matrix metalloproteinases. |
| ジャーナル | Sci Signal |
| Abstract |
The tumor microenvironment can enhance the invasive capacity of tumor cells. We showed that expression of angiopoietin-like protein 2 (ANGPTL2) in osteosarcoma (OS) cell lines increased and the methylation of its promoter decreased with time when grown as xenografts in mice compared with culture. Compared with cells grown in normal culture conditions, the expression of genes encoding DNA demethylation-related enzymes increased in tumor cells implanted into mice or grown in hypoxic, serum-starved culture conditions. ANGPTL2 expression in OS cell lines correlated with increased tumor metastasis and decreased animal survival by promoting tumor cell intravasation mediated by the integrin α5β1, p38 mitogen-activated protein kinase, and matrix metalloproteinases. The tolloid-like 1 (TLL1) protease cleaved ANGPTL2 into fragments in vitro that did not enhance tumor progression when overexpressed in xenografts. Expression of TLL1 was weak in OS patient tumors, suggesting that ANGPTL2 may not be efficiently cleaved upon secretion from OS cells. These findings demonstrate that preventing ANGPTL2 signaling stimulated by the tumor microenvironment could inhibit tumor cell migration and metastasis. |
| 巻・号 | 7(309) |
| ページ | ra7 |
| 公開日 | 2014-1-21 |
| DOI | 10.1126/scisignal.2004612 |
| PII | 7/309/ra7 |
| PMID | 24448647 |
| MeSH | Angiopoietin-Like Protein 2 Angiopoietin-like Proteins Angiopoietins / genetics Angiopoietins / physiology* Animals Bone Neoplasms / enzymology Bone Neoplasms / metabolism Bone Neoplasms / pathology Cell Line, Tumor DNA Methylation Heterografts Humans Integrin alpha5beta1 / metabolism* Matrix Metalloproteinases / metabolism* Mice Neoplasm Metastasis Neovascularization, Pathologic Osteosarcoma / enzymology Osteosarcoma / metabolism Osteosarcoma / pathology* Promoter Regions, Genetic Tumor Microenvironment p38 Mitogen-Activated Protein Kinases / metabolism* |
| IF | 6.467 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 17 |
| 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 | Saos-2(RCB0428) 143B/TK^(-)neo^(R)(RCB0701) |