Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions.
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| 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.
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| Authors | Katsuaki Ieguchi, Takeshi Tomita, Toshifumi Takao, Tsutomu Omori, Taishi Mishima, Isao Shimizu, Massimiliano Tognolini, Alessio Lodola, Takuya Tsunoda, Shinichi Kobayashi, Satoshi Wada, Yoshiro Maru |
| Journal | International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 5 (Mar 01 2021) ISSN: 1422-0067 [Electronic] Switzerland |
| PMID | 33804570 (Publication Type: Journal Article) |
| Chemical References |
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