Pathogenesis of interactions between CD8-positive T cells and cancer fibroblasts in the renal cell carcinoma microenvironment.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hiroshima University
• Principal Investigator: Kitano Hiroyuki 広島大学, 病院(医), 助教 (60721933)
• Co-Investigator(Kenkyū-buntansha): 北台 靖彦 県立広島大学, 人間文化学部, 教授 (10304437) ; 仙谷 和弘 広島大学, 医系科学研究科(医), 講師 (30508164) ; 弓削 亮 広島大学, 病院(医), 講師 (70794791)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 癌線維芽細胞 / 癌微小環境 / Nesprin1

Outline of Final Research Achievements

Co-culture of renal cancer cell lines with MSCs increased cell proliferation and migration. The luciferase- and GFP-expressing human renal carcinoma cell line Caki-1 was used in an orthotopic transplantation model of mice, which were divided into a control group (group C) and an MSC group injected via the tail vein. Immunostaining of excised tumors confirmed that MSCs differentiated into fibroblasts, and Caki-1 significantly enhanced cell proliferation and migration when co-cultured with MSCs. Nesprin1-negative tumors had shorter OS, CSS, and PFS. Deletion of Nesprin1 in renal carcinoma contributes to increased invasive and migratory potential.

Free Research Field

腎細胞癌

Academic Significance and Societal Importance of the Research Achievements

腎細胞癌において癌線維芽細胞は骨髄由来のstem cellから分化する可能を明らかにし、Nesprin1という分子がその発現により腎細胞癌の生存期間や非再発率を増加する事を明らかにした。そのため骨髄由来stem cellやNesprin1は腎細胞癌の治療標的となる可能性があると思われる。特にNesprin1は口腔がんや胃癌、肺がん、肝細胞癌、また新血管系疾患など癌だけではなく良性疾患においてもその機能が注目されており、癌治療だけではなく良性疾患での治療標的にもなる可能性が考えられた。