Identification of responsible genes of dissemination of gastric canncer using induced cancer stem-like cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17692
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: Nishiyama Mitsuo 山口大学, 医学部附属病院, 診療助教(4日/週) (50714614)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌

Outline of Final Research Achievements

We induced cancer stem-like sphere cells (CSLCs) from a human gastric cancer cell line, MKN45, using unique CSLC induction medium and examined the expression of cancer stem cell marker (CD44v), peritoneal dissemination, anticancer drug resistance, and gene expression profile. The results showed that CSLCs with elevated expression of cancer stem cell marker CD44v were induced from human gastric cancer cell line MKN45, and these CSLCs showed increased frequency of peritoneal dissemination and resistance to anti-cancer drugs (5-fluorouracil and irinotecan). Furthermore, similar to the previously reported liver-CSLCs, the CSLCs showed enriched gene sets related to epithelial-mesenchymal transition and hypoxia, as well as increased expression of HLA and MICA/B, which are involved in escape from the innate immune system.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

胃癌実臨床上の大きな課題の一つに腹膜播種再発が挙げられる。播種再発の抑制は胃癌治療成績向上の重要な鍵といえる。我々は独自にがん幹細胞様細胞 (CSLC) を有しており、胃がん細胞株から誘導したCSLCは、腹膜播種頻度の増加だけでなく、抗がん剤耐性も上昇を示した。さらに、遺伝子発現プロファイルを検討したところ、転移過程において重要な自然免疫系からの逃避を示した肝がんCSLCと同様のプロファイルを有することが示唆された。本研究による胃がん腹膜播種機構に対する検討は、今後の胃がん予後の改善につながる学術的・社会的意義を有する成果が得られた。