Clarifying the mechanism of epithelial to mesenchymal transition in brain tumors

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K16595
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: NAGAISHI MASAYA 獨協医科大学, 医学部, 准教授 (40364632)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 上皮間葉系移行 / 神経膠腫 / ZEB / MMP9

Outline of Final Research Achievements

In this study, we identified that epithelial-mesenchymal transition mechanism is associated with the transition to a sarcoma-like phenotypic, dissemination, and metastasis of glioblastoma cells. In addition to the transcription factors Slug and TWIST, which have previously been implicated, the high expression of ZEB2 was found in glioblastoma cells. MMP9 was considered to act as a downstream factor of Slug, TWIST and ZEB2. The cadherin switching is considered to the important mechanism causing the reduce of intercellular adhesion in tumor invasion, but not in the phenotypic transformation of glioblastomas.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

腫瘍細胞が他臓器へ転移、浸潤するには、浸潤先の環境に適応する必要がある。細胞自体の形質を転換する上皮間葉系移行は、この環境適応のために重要なメカニズムの一つと考えられている。本研究の結果は、脳悪性腫瘍の代表である神経膠腫において、この間葉系メカニズムが腫瘍浸潤に関与していることを示唆した。上皮間葉系移行関連転写因子である、Slug, TWIST, ZEB2、その下流因子であるMMP9が重要因子として同定された。腫瘍浸潤に関連する分子同定は、将来の分子標的治療へと繋がる研究結果である。