RNA modification affecting lymph node metastasis in esophageal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09048
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Akita University
• Principal Investigator: Motoyama Satoru 秋田大学, 医学系研究科, 非常勤講師 (60292372)
• Co-Investigator(Kenkyū-buntansha): 久場 敬司 秋田大学, 医学系研究科, 非常勤講師 (10451915)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: リンパ節転移 / Galectin / 腫瘍免疫

Outline of Final Research Achievements

Lymph node (LN) metastasis predicts poor prognosis in esophageal cancer patients, whereas the underlying mechanisms remain. Using a syngeneic mouse squamous cell carcinoma (SCC) model of NR-S1M cells, we isolated metastasized NR-S1M cells from LNs in tumor-bearing mice and established metastatic NR-S1M cells in in vitro culture. RNA-seq analysis revealed that interferon gene signature was markedly downregulated in metastatic NR-S1M cells compared with parental cells, and in vivo NR-S1M tumors heterogeneously developed focal immunosuppressive areas featured by deficiency of anti-tumor immune cells. Spatial transcriptome analysis (Visium) for the NR-S1M tumors revealed that Galectin-7 was a novel metastasis-driving factor. Deletion of Galectin-7 in NR-S1M cells significantly suppressed LN metastasis without affecting primary tumor growth. Galectin-7 is a new crucial mediator LN metastasis.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

RNA-Seq及びVisium空間的トランスクリプトーム解析から見出したGalectin分子が癌リンパ節転移における重要な因子であることが示唆された。近年、がん抗原ワクチン療法、免疫チェックポイント阻害療法、CAR-T療法の開発など、癌治療において腫瘍免疫学は最も期待されている分野である。本研究におけるGalectin分子の免疫抑制分子機序の解明は、腫瘍免疫学分野からの新たなリンパ節転移治療法の開発につながる重要な基礎研究になる。