Study on human prostate carcinogenesis by using cancer progenitor cells and application for the new molecular target

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293079
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: Konishi Noboru 奈良県立医科大学, 医学部, 教授 (20145832)
• Co-Investigator(Kenkyū-buntansha): 藤本 清秀 奈良県立医科大学, 医学部, 教授 (50264867) ; 藤井 智美 奈良県立医科大学, 医学部, 講師 (50623477) ; 島田 啓司 奈良県立医科大学, 医学部, 研究員 (90336850)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 前立腺癌 / 癌始原細胞 / cancer progenitor cells / Syndecan-1 / heparanase / autophagy / TRAMPマウス

Outline of Final Research Achievements

Heparanase-an enzyme that activates syndecan-is overexpressed in PIA lesions and contributes to the differentiation of basal cells to intermediate cells. Heparanase also suppressed the induction of autophagy by enhancing STAT3 phosphorylation in human prostatic epithelial cells at different passages by which carcinogenetic process could be executed in human prostate. Immunohistochemistry data for autophagy-related molecules, such as LC3, support the in vitro data. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, early intervention with a syndecan-1 inhibitor reduced the incidence of adenocarcinoma. Antibody for syndecan-1 produced in this study was immunoreactive, but not cytotoxic. Heparanase may play important roles in the neoplastic transformation of intermediate cells in response to regulation of autophagy, and thus indicate that heparanase may be a molecular target for prostate cancer therapy and chemoprevention.

Free Research Field

人体病理学