Elucidation of the mechanism of lung metastasis activation by lymph node dissection for oral cancer and development of the preventive methods

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10303
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tohoku University
• Principal Investigator: Miyashita Hitoshi 東北大学, 大学病院, 講師 (70372323)
• Co-Investigator(Kenkyū-buntansha): 森 士朗 東北大学, 大学病院, 講師 (80230069)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: リンパ節郭清 / リンパ節腫脹マウス / リンパ節転移モデルマウス / 肺微小転移 / 休眠細胞活性化

Outline of Final Research Achievements

Using a mouse model of lung metastasis, MXH10/Mo/lpr, in which micro-metastasis of the lung is activated by ablation of the lymph node (LN), a large amount of proteomic data were obtained by serum mass spectrometry analysis of molecules involved in the activation of lung metastasis with serum took before and after the activation. However, identification of the molecules involved has not been achieved. On the other hand, in the course of our study, it was found that doxorubicin-encapsulated liposomes (DOX-LP) injected into metastatic LNs and irradiated with ultrasound could inhibit the activation of the above-mentioned pulmonary micrometastases. We are currently investigating new strategies to elucidate the mechanism by which lung micrometastases are activated by resection of LNs in tumor-bearing mice and inactivated by intra-LN injection of DOX-LP and ultrasound irradiation.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

肺転移は頭頸部癌を含む多くの癌において生命予後を規定する極めて重要な因子であり、肺転移の予防法の開発は癌患者の治療成績の向上に極めて重要である。本研究では、担癌マウスのリンパ節(LN)の切除により肺転移が活性化する病因解明を血清質量分析法を用いて試みたが肺転移の活性化に関与する分子の同定には至らなかった。しかし、ドキソルビシン封入リポソーム(DOX-LP)を転移LNに注入し超音波照射することにより上記肺微小転移の活性化を抑制する新たな肺転移の病態解析モデルを樹立した。この研究モデルにより肺転移病巣の活性化抑制のための治療法の開発に新たな方向性を示すことができた。