マル ヨシロウ   Maru Yoshiro
  丸 義朗
   所属   医学部 医学科
   職種   教授・基幹分野長
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions.
掲載誌名 正式名:International journal of molecular sciences
略  称:Int J Mol Sci
ISSNコード:14220067/14220067
掲載区分国外
巻・号・頁 22(5),pp.2480
著者・共著者 Ieguchi Katsuaki, Tomita Takeshi, Takao Toshifumi, Omori Tsutomu, Mishima Taishi, Shimizu Isao, Tognolini Massimiliano, Lodola Alessio, Tsunoda Takuya, Kobayashi Shinichi, Wada Satoshi, Maru Yoshiro
担当区分 最終著者
発行年月 2021/03
概要 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.
DOI 10.3390/ijms22052480
PMID 33804570