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

Yamaguchi, Miki, Hirai, Sachie, Sumi, Toshiyuki, Tanaka, Yusuke, Tada, Makoto, Nishii, Yukari, Hasegawa, Tadashi, Uchida, Hiroaki, Yamada, Gen, Watanabe, Atsushi, Takahashi, Hiroki, Sakuma, Yuji
Biochemical and biophysical research communications 2017 v.487 pp. 613-618
adenocarcinoma, antineoplastic agents, epithelial cells, mice, monoclonal antibodies, neoplasm cells, peptidyl-dipeptidase A
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.