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Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant lung adenocarcinoma

Author:
Yamaguchi, Miki, Hirai, Sachie, Sumi, Toshiyuki, Tanaka, Yusuke, Tada, Makoto, Nishii, Yukari, Hasegawa, Tadashi, Uchida, Hiroaki, Yamada, Gen, Watanabe, Atsushi, Takahashi, Hiroki, Sakuma, Yuji
Source:
Biochemical and biophysical research communications 2017 v.487 pp. 613-618
ISSN:
0006-291X
Subject:
adenocarcinoma, antineoplastic agents, epithelial cells, mice, monoclonal antibodies, neoplasm cells, peptidyl-dipeptidase A
Abstract:
EGFR-mutant lung adenocarcinomas contain a subpopulation of cells that have undergone epithelial-to-mesenchymal transition and can grow independently of EGFR. To kill these cancer cells, we need a novel therapeutic approach other than EGFR inhibitors. If a molecule is specifically expressed on the cell surface of such EGFR-independent EGFR-mutant cancer cells, it can be a therapeutic target. We found that a mesenchymal EGFR-independent subline derived from HCC827 cells, an EGFR-mutant lung adenocarcinoma cell line, expressed angiotensin-converting enzyme 2 (ACE2) to a greater extent than its parental cells. ACE2 was also expressed at least partially in most of the primary EGFR-mutant lung adenocarcinomas examined, and the ACE2 expression level in the cancer cells was much higher than that in normal lung epithelial cells. In addition, we developed an anti-ACE2 mouse monoclonal antibody (mAb), termed H8R64, that was internalized by ACE2-expressing cells. If an antibody-drug conjugate consisting of a humanized mAb based on H8R64 and a potent anticancer drug were produced, it could be effective for the treatment of EGFR-mutant lung adenocarcinomas.
Agid:
5675804