論文 - 詳細
| RRC ID | 67506 |
|---|---|
| 著者 | Ieguchi K, Tomita T, Takao T, Omori T, Mishima T, Shimizu I, Tognolini M, Lodola A, Tsunoda T, Kobayashi S, Wada S, Maru Y. |
| タイトル | Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Accumulating evidence indicates that an elevated ephrin-A1 expression is positively correlated with a worse prognosis in some cancers such as colon and liver cancer. The detailed mechanism of an elevated ephrin-A1 expression in a worse prognosis still remains to be fully elucidated. We previously reported that ADAM12-cleaved ephrin-A1 enhanced lung vascular permeability and thereby induced lung metastasis. However, it is still unclear whether or not cleaved forms of ephrin-A1 are derived from primary tumors and have biological activities. We identified the ADAM12-mediated cleavage site of ephrin-A1 by a Matrix-assisted laser desorption ionization mass spectrometry and checked levels of ephrin-A1 in the serum and the urine derived from the primary tumors by using a mouse model. We found elevated levels of tumor-derived ephrin-A1 in the serum and the urine in the tumor-bearing mice. Moreover, inhibition of ADAM-mediated cleavage of ephrin-A1 or antagonization of the EphA receptors resulted in a significant reduction of lung metastasis. The results suggest that tumor-derived ephrin-A1 is not only a potential biomarker to predict lung metastasis from the primary tumor highly expressing ephrin-A1 but also a therapeutic target of lung metastasis. |
| 巻・号 | 22(5) |
| 公開日 | 2021-3-1 |
| DOI | 10.3390/ijms22052480 |
| PII | ijms22052480 |
| PMID | 33804570 |
| PMC | PMC7957476 |
| MeSH | ADAM12 Protein / genetics ADAM12 Protein / metabolism* Animals Capillary Permeability Carcinoma, Lewis Lung / genetics Carcinoma, Lewis Lung / metabolism Carcinoma, Lewis Lung / pathology* Ephrin-A1 / genetics Ephrin-A1 / metabolism* HEK293 Cells Humans Mice Mice, Inbred C57BL Neoplasm Metastasis Receptor, EphA2 / genetics Receptor, EphA2 / metabolism* Tumor Cells, Cultured |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | LLC(RCB0558) |