Search for target molecules based on comprehensive analysis of functional gain in mechanisms of cancer-associated stromal cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09182
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kagoshima University
• Principal Investigator: Ueda Kazuhiro 鹿児島大学, 医歯学総合研究科, 特任准教授 (90420520)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌関連間質細胞 / 細胞外マトリックス / 接着分子

Outline of Final Research Achievements

The purpose of this study was to elucidate the characteristic acquisition mechanism of stromal cells in cancer tissue and to clarify therapeutic target molecules for stromal cells. Specifically, three fresh tissue specimens were collected from 35 surgical specimens, i.e., internal, adjacent, and distant cancer tissues, and stromal cells were cultured to amplify stromal cells. Adherent cells (not cancer cells) of the second generation were collected. Cells stained with both vimentin and cytokeratin were observed by fluorescence immunostaining. cDNA expression was examined by PCR using the RT2 PROFILER kit containing candidate extracellular matrix and adhesion molecules. We found candidate molecules that were highly expressed in the central part of the cancer compared to the peripheral and distant parts of the cancer, and focused on COL11A1, which was highly expressed in all 4 cases.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤は注目されているが治療効果を鋭敏に予測できる特異性なバイオマーカーは特定されていない。バイオマーカーの探索においては癌細胞に限定するのではなく癌の微小環境を対象に入れた探索を行う必要がある。免疫細胞（マクロファージ）、間質細胞の働きにより細胞障害性T細胞の活性を抑制し、制御性T細胞の浸潤を促すことで抗腫瘍免疫が抑制されると考えられている。本研究により明らかとなった間質細胞の標的遺伝子異常（COL11A1）は、新しい標的治療の開発の突破口となることが期待される。さらに、将来的には免疫チェックポイント阻害療法の適応を決める有用なバイオマーカーとなる可能性もある。