Innovative treatment of refractory digestive cancers based on the stemness visualization system

2015 Fiscal Year Final Research Report

• Project/Area Number: 25253081
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tanaka Shinji 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30253420)
• Co-Investigator(Kenkyū-buntansha): MORI Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999) ; NAKAMURA Noriaki 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (10372442) ; AIHARA Arihiro 東京医科歯科大学, 医学部附属病院, 助教 (90451939) ; AKIYAMA Yoshimitsu 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (80262187) ; SHIMADA Shu 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20609705)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 癌 / 幹細胞 / トランスレーショナルリサーチ / 転移 / 治療標的 / がん予防 / 外科 / 再生医学

Outline of Final Research Achievements

A real-time visualization system for cancer stem cells (CSCs) was established (Clin Cancer Res, in press). We found that human pancreatic CSCs were highly metastatic and dominantly localized at the invading margins in liver metastasis. Microarray and siRNA screening assays showed that DCLK1 was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, the specific expression of DCLK1 was detected in the metastatic tumors in patients with pancreatic cancer. Our studies identified DCLK1, that is essential for the metastatic properties of CSCs, as a promising epigenetic and therapeutic target in human pancreatic cancer (PLoS One 2016). In addition, we revealed transgenic mice with this system are useful for cancer prevention strategies.

Free Research Field

消化器外科学、分子腫瘍医学