Establishment of novel treatment strategy for oral cancer using patient-derived in vitro model with heterogeneous characters

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03892
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Yokohama City University
• Principal Investigator: Kioi Mitomu 横浜市立大学, 附属病院, 准教授 (30545059)
• Co-Investigator(Kenkyū-buntansha): 谷口 英樹 横浜市立大学, 医学研究科, 客員教授 (70292555)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 口腔がん / オルガノイド / ドラッグスクリーニング

Outline of Final Research Achievements

Tumor microenvironment (TME) plays crucial roles in tumor progression and treatment resistance. Thus, it is extremely important to find its role involved in the interaction of TME. The purpose of this study is to develop stroma cells-incorporating preclinical model, termed TME mimic oral cancer organoid. We have first developed the organoid by selecting the stroma cells such as endothelial cells, fibroblast, ratio of those cells, culture method, 3-D methods, culture media, and supplement of growth factors. Then, growth rate, morphology, radiosensitivity, and drug response were analyzed to investigate the effect of TME. Oral cancer cells were co-cultured with endothelial cells and mesenchymal stem cells in a particular ratio in 3D-culture, and the formed organoid became sphere. The vascular formation in the organoid was confirmed by immunofluorescent analysis. OSC-19luc organoid was resistance to cisplatin compared to 3D-cultured OSC-19luc alone or OSC-19-luc co-cultured with ECs/MSCs.

Free Research Field

がん研究

Academic Significance and Societal Importance of the Research Achievements

本研究では、口腔がんの治療抵抗性を克服する多剤併用の新規治療戦略を開発するため、癌細胞の不均一性や微小環境などの臨床的有用性を有する患者由来口腔がんオルガノイドの確立とドラッグスクリーニングへの応用を行う。