Elucidation of the metastasis mechanism of oral cancer and development of the new therapeutics based on tumor dormancy of bone marrow-disseminated tumor cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20594
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: Nakamura Takuya 熊本大学, 医学部附属病院, 非常勤診療医師 (80761212)
• Research Collaborator: MATSUI Hirotaka 熊本大学, 大学院生命科学研究部, 教授 (60379849) ; SHINRIKI Satoru 熊本大学, 大学院生命科学研究部, 准教授 (00583048)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 休眠状態 / 骨髄播種癌細胞 / 抗癌剤耐性 / 骨髄環境 / TG-β2 / 増殖抑制状態

Outline of Final Research Achievements

Dormant disseminated tumor cells (DTC) in bone marrow (BM) are resistant to conventional therapy in　cancers including head and neck squamous cell carcinoma (HNSCC). This study aimed to elucidate intrinsic molecular characteristics in BM-DTC. We used the human HNSCC cell line HEp3-originated sublines [i.e. parental line (P-HEp3), BM-DTC-derived (BM-HEp3), and lung metastases-derived sublines (Lu-HEp3)]. We revealed that the TGF-β2-SDF-1-CXCR4 signaling axis was crucial for drug resistance dependent on a slow-cycling state in BM-DTC but not in lung metastatic cells. Our analyses revealed that slow-cycling and drugresistant BM-HEp3 cells had unique gene expression signatures. In addition, our investigation for phosphorylation of 39 kinases associated with tumor progression showed enhanced activation of only Src in BM-HEp3 compared with P- and Lu-HEp3. Further studies should contribute to better understanding of biology of tumor cell dormancy and minimal residual disease in BM.

Free Research Field

口腔外科