Analysis of in vivo niches and therapeutic targets for cancer stem cells based on the visualization mechanism

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15491
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tanaka Shinji 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30253420)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 癌 / 幹細胞 / 膵腫瘍 / 免疫チェックポイント / ゲノム編集 / 分子標的剤 / トランスレーショナルリサーチ / 癌抑制遺伝子

Outline of Final Research Achievements

Identification and purification of cancer stem cells (CSCs) lead to the discovery of novel therapeutic molecules of pancreatic neuroendocrine tumor (pNET). In this study, we identified CD73 overexpressed in pNET CSCs. The CD73-inhibitor APCP significantly attenuated in vitro sphere formation and cell motility, as well as in vivo tumorigenicity of pNET CSCs. Immunohistochemical analysis of clinical samples demonstrated CD73 expression was significantly correlated with the tumor invasion.
In addition, our genome editing studies revealed that pNET can acquire CSC potentials with tumorigenicity by knockout of tumor suppressor gene X. We identified "Y" as one of the direct targets of tumor suppressor X. In clinical samples, significantly frequent recurrence was recognized in pNETs with low X and high Y expression.
Recently, CD73 was reported as a potential inducer of PD-1 immune checkpoint factor. As a result of our studies, CD73 and Y might be promising therapeutic targets for pNET.

Free Research Field

分子腫瘍医学、消化器外科学