Identification of tumor stroma-related genes in head and neck cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18736
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Yorozu Akira 札幌医科大学, 医学部, 研究員 (20792120)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 頭頚部癌 / 癌間質 / AEBP1 / ACLP / CAF

Outline of Final Research Achievements

First, we analyzed the expression levels of AEBP1 in oral squamous cell cancer (OSCC) by immunohistochemical staining of 49 clinical specimens. As a result, we confirmed that AEBP1 is significantly upregulated in cancer associated fibroblast (CAF) cells in tumor tissues and expression levels of AEBP1 is associated with tumor size, clinical stage, histological grade, and prognosis of OSCC patients. The expression of AEBP1 was induced by treatment of TGF-β or co-culture with OSCC cells, and depletion of AEBP1 in CAF cells inhibited migration ability and invasiveness of co-cultured OSCC cells. Additionally, we demonstrated that AEBP1 induced upregulation of several EMT related genes including vimentin and overexpression of AEBP1 in CAF cells promoted invasion of OSCC cells and tumor forming ability in mouse xenograft model.

Free Research Field

頭頚部がん

Academic Significance and Societal Importance of the Research Achievements

AEBP1のがん間質における働きについて、いまだ研究報告はわずかである。本研究により、AEBP1が頭頸部扁平上皮がんのCAFにおいて高発現すること、CAFにおけるAEBP1の発現は、癌細胞との共培養やTGF-β刺激により誘導されること、がん細胞の遊走・浸潤・転移の促進や、腫瘍免疫の抑制に関わることが明らかになった。今後、CAFやがん細胞においてAEBP1と相互作用する分子の同定、腫瘍間質と免疫細胞の相互作用におけるAEBP1の機能解析など、AEBP1の作用機構を解明することで、頭頚部扁平上皮がんの新規治療法の開発につながることが期待される。