Analysis of the chemotherapy resistance by copper transporters using X-ray Fluorescence to evaluate the copper distribution.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16387
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyushu University
• Principal Investigator: KOBA Ryo 九州大学, 医学研究院, 共同研究員 (10866776)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 食道癌 / 白金製剤 / 銅輸送体 / 蛍光X線分析 / 腫瘍微小環境

Outline of Final Research Achievements

This study was started to elucidate the mechanism of the chemotherapy resistance related to copper transporters by evaluating the copper distribution in esophageal cancer treated with Cisplatin. To assess which cells expressed the copper transport related genes (encoded by CTR1/2), we performed a comprehensive analysis using single-cell RNA sequence data, which were available in our laboratory. Analysis of 6 esophageal cancer samples treated with neoadjuvant chemotherapy revealed that macrophages expressed the CTR1/2 genes higher than stromal cells such as fibroblasts. Moreover, comparing PD groups with SD/PR groups, macrophages in PD groups downregulated CTR2 genes. In short, these data suggest that macrophages in esophageal cancer may relate to the chemotherapy resistance.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究は食道癌における白金錯体系抗腫瘍薬への抵抗性獲得の機序として銅輸送体に着目し、白金製剤投与後の銅輸送体の各細胞における発現度や銅の局所的な分布を評価することで化学療法治療抵抗性の機序を解明することを目的とした。シングルセル解析を行うことで、網羅的かつ単一細胞レベルでの詳細な発現解析が可能であった。従来、線維芽細胞などの間質細胞が白金製剤抵抗性に寄与していると考えられていたが、本研究によりマクロファージが関連していることが示唆され、今後治療抵抗性獲得機序の解明における一助となりうると考えられた。