Analysis of effect and resistance of molecular-targeted therapy in renal cell carcinoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Keio University
• Principal Investigator: Mikami Shuji 慶應義塾大学, 医学部, 講師 (20338180)
• Co-Investigator(Kenkyū-buntansha): KOSAKA TAKEO 慶應義塾大学, 医学部, 講師 (30445407) ; MIZUNO RYUICHI 慶應義塾大学, 医学部, 講師 (60383824)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 腎細胞癌 / 浸潤 / 転移 / 分子標的治療 / 癌幹細胞 / 上皮－間葉転換

Outline of Final Research Achievements

This study was performed to clarify the significance of TNF-α and CD44 in clear cell renal cell carcinomas (ccRCCs). Co-upregulation of TNF-α and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-α enhanced migration and invasion of ccRCC cells together with down-regulation of E-cadherin expression and up-regulation of matrix MMP9 and CD44 expression. Among ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-α plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-α may be involved in the resistance to the sunitinib treatment.

Free Research Field

病理学