Integrative analyses of lung adenocarcinomas that have undergone epithelial to mesenchymal transition (EMT) and those that retain an epithelial phenotype

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08364
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: Sakuma Yuji 札幌医科大学, 医学部, 准教授 (10364514)
• Co-Investigator(Kenkyū-buntansha): 山口 美樹 札幌医科大学, 医学部, 助教 (10530454)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 肺腺癌 / 上皮間葉移行 / EGFR / 薬剤耐性

Outline of Final Research Achievements

EGFR-mutant lung adenocarcinomas depend on the kinase for survival. We have identified a new molecular mechanism that contributes to TKI resistance, and a previously unrecognized membranous molecule TKI-resistant cancer cells selectively express. (1) The EGFR mutant lung adenocarcinoma cell line, H1975, has a subset of cells that exhibits an EMT phenotype and can thrive in the presence of EGFR TKIs. These cells depend on the isomerase Pin1 for survival in vitro, unlike their parental cells. (2) A mesenchymal EGFR-independent subline derived from the EGFR mutant lung adenocarcinoma cell line, HCC827, expressed ACE2 to a greater extent than its parental cells. We also 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.

Free Research Field

病理学