Development of a multidisciplinary anti-metastasis treatment against lymph node metastasis of head and neck squamous cell carcinomas

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09379
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Ehime University
• Principal Investigator: Yano Hajime 愛媛大学, 医学系研究科, 准教授 (00284414)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 頭頚部扁平上皮がん / リンパ節転移 / リジルオキシダーゼ / ナトリウムイオン / プロトン交換輸送体１ / 細胞外小胞 / エクソソーム / 患者血清エクソソーム

Outline of Final Research Achievements

Cancer metastases are multi-factorial as well as multi-dimensional events. This study was aimed at proving multidisciplinary treatment against factors responsible for metastases is effective on "anti-metastasis" therapy. We have reported that one of the target molecules of the multidisciplinary treatment, LOXL localizes to exosomal fraction derived from the Head and Neck Squamous Cell Carcinoma (HNSCC) both in cultured cells as well as serum from patients. Amounts of LOXL2 were higher in relatively early phase of the HNSCC patients suggesting the participation of LOXL2 on the early phase of metastasis. The HNSCC cell with double knockdown of LOXL2 together with another target protein NHE1 exhibited decreased primary engraftment to non-tumor tissues, makes the HNSCC cell, possibly, much less metastatic than each single knockdown.

Free Research Field

がん転移

Academic Significance and Societal Importance of the Research Achievements

血清エクソソーム様画分に注目することで、リンパ節転移がないか少ない比較的初期の頭頸部がん患者においてLOXL2 含量が亢進していることが示された。動物実験においては LOXL2 がリンパ節転移に寄与することはすでに確認されていたので、それを肯定的に支持する患者血清データが得られたことの臨床的意義は大きい。一方 NHE1 / LOXL2 両ノックダウン細胞のマウス舌移植における生着性の低下はこれまで各因子の単独ノックダウンにおいては観察されておらず、目指していた相加的な抗-転移性のみならず、さらに強い相乗的抗-転移性が生じている可能性がある。