Establishment of in vitro human gastric signet-ring carcinogenesis model.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyushu University
• Principal Investigator: Ariyama Hiroshi 九州大学, 大学病院, 助教 (80713437)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃印環細胞がん / E-cadherin / CXCR4 / MMP3

Outline of Final Research Achievements

We succeeded in culture of gastric stem cell from surgical specimen in vivo. Gastric stem cell differentiated into pit cells, mucous neck cells, chief cells and G cells, but not parietal cells. We detected signet-ring cells after knock out of E-cadherin by using CRISPR-Cas9 system in organoid cells. These cells showed higher mobility than normal organoid cells. MMP3 is associated with this cell mobility. We also detected CXCR4 in the nucleus in normal organoid cells, but CXCR4 was translocated from the nucleus to cellular membrane after E-cadherin knock out. Apoptosis was induced by AMD3100, which is the inhibitor of CXCR4-CXCL12 axis. MMP3 and CXCR4 could be therapeutic targets of signet-ring cell carcinoma.

Free Research Field

腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

胃印環細胞がんは若年女性に多く、高い運動性に基づき早期に転移、特に腹膜播種をきたす予後不良な疾患である。今回我々は印環細胞がんをin vitroで作成することに成功し、その高い運動性にMMP3が関与することを確認した。またCXCR4からのシグナルをブロックすることにより印環細胞にアポトーシスが誘導されることを確認し、印環細胞の新たな治療ターゲットとして期待される薬物と考えられた。これらの結果は予後不良な胃印環細胞がんの新たな治療法開発に役立つものと考える。