Visualization of cancer-initiating cells and search for an effective treatment using gastric cancer organoids

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07161
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Murakami Kazuhiro 金沢大学, がん進展制御研究所, 助教 (60455368)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: がん幹細胞 / 胃がん / オルガノイド / LGR5

Outline of Final Research Achievements

Our goal is to establish an effective treatment for gastric cancer. By using newly established mouse and human gastric cancer organoids, we tried to identify cancer-initiating cells and clarify the mechanism which induce their malignancy. Furthermore, based on knowledges, we searched for an effective treatment for gastric cancer in vivo. We proceeded our research with focusing on an epithelial stem cell marker, LGR5 and found that LGR5 positive gastric cancer cells could be the cancer-initiating cell. By a comprehensive gene expression analysis, we found a group of genes which could regulate proliferation and maintenance of cancer-initiating cells. We orthotopically transplanted genetically modified organoids into mouse stomach and found that some genes can regulate the metastatic ability of cancer-initiating cells. Furthermore, we found drug candidates which can selectively eliminate cancer-initiating cells.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

胃がんは肺がんと並びがんによる死因の多くを占める。がんの再発と転移の背景には治療抵抗性を持つがん幹細胞の存在が示唆されており、がんの根絶に向けてがん幹細胞の増殖能・分化能を抑制しつつ、がん全体を標的とする治療法の確立が急務となっている。しかし、胃におけるがん幹細胞の正体は明らかになっておらず、そのため悪性度の高い胃がんに対する真に効果的な治療法の確立には至っていない。本研究では、胃がん幹細胞の同定と増殖性・可塑性・分化能を制御する機構の解明を通して、胃がんを根絶する真に効果的な治療法の確立へ貢献する。