| 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
|
| リソース情報 |
| ヒト・動物細胞 |
LLC(RCB0558) |
