Analysis of Cancer cell death induced by "Death-touch"

2016 Fiscal Year Final Research Report

• Project/Area Number: 26640068
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Akita University
• Principal Investigator: Tanaka Masamitsu 秋田大学, 医学(系)研究科(研究院), 教授 (20291396)
• Co-Investigator(Renkei-kenkyūsha): KURIYAMA SEI 秋田大学, 医学部, 准教授 (30398226) ; ITOH GO 秋田大学, 医学部, 助教 (60607563)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: スキルス胃癌 / 癌関連線維芽細胞 / CAF / アポトーシス

Outline of Final Research Achievements

We found that CAFs induce apoptosis in gastric cancer cells, which switches the invasion mode of tumors. Death receptor 4 and activation of caspase-8 in cancer cells mediated cancer cell apoptosis induced by CAFs, which was dependent on contact between cancer cells and CAFs. Apoptotic cancer cells in turn released apoptotic vesicles and stimulated invasion of CAFs. Accordingly, cancer cells followed the migrating CAFs. Treatment with a caspase inhibitor, ZVAD, or forced expression of a death domain (DD) fragment in cancer cells prevented cancer cell apoptosis induced by CAFs and increased expansive invasion by cancer cells in extracellular gel invasion assays, while the rate of cancer cell invasion led by CAFs was decreased. Because CAF-led invasion is characterized by the movement of individual cancer cells away from the tumor, adequate cancer cell apoptosis may promote cancer dissemination.

Free Research Field

腫瘍生物学