Functional analysis of TMEM2, a novel hyaluronidase involved in bladder cancer invasion and metastasis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16724
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hirosaki University
• Principal Investigator: Yoneyama Mihoko 弘前大学, 医学研究科, 客員研究員 (50791696)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: TMEM2 / ヒアルロン酸代謝 / EMT / 膀胱癌

Outline of Final Research Achievements

transmembrane protein 2 (TMEM2), which serves as a reportedly functions in malignancy of several solid tumors. We investigate potential changes in expression of TMEM2 during bladder cancer (BCa) invasion and over the course of the epithelial mesenchymal transition (EMT). Immunohistochemical analysis revealed that TMEM2 expression changed with pathological stage (pT) and infiltration pattern (INF) and was highest in pTa-pT1 of INFa tumors and significantly lower at stages from pTa-pT1 to pT2 or 3 in INFb or INFc. BCa cell lines showed that muscle-invasive cells with low TMEM2 expression exhibited EMT phenotypes in vitro, in contrast to high TMEM2-expressing non-muscle invasive cells. EMT-induced non-muscle invasive cells also showed significantly decreased plasma membrane expression of TMEM2. Our data suggested TMEM2 expression is higher in non-invasive cancers, whereas invasive cancer cells are less likely to express TMEM2 during muscle-invasion and "partial EMT".

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

癌微小環境におけるヒアルロン酸の分子サイズは癌の増殖、浸潤に影響を与える。本研究の成果によって、高分子ヒアルロン酸を分解するTMEM2が膀胱上皮に発現していること、また悪性度の低い癌やクラスターを形成する癌で高発現である一方、浸潤性の高い癌では低下していることが明らかとなった。本研究成果によって、これまでのヒアルロン酸分解における定説であったHYAL依存的な古典的分解経路とCEMIP/KIA1199による分解経路だけでは説明しきれなかった代謝機構を考えるための手がかりとなりうる。