Development of molecular target agents for oral cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K11271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tokyo Dental College
• Principal Investigator: Takano Nobuo 東京歯科大学, 歯学部, 客員教授 (30147219)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 口腔癌 / 扁平上皮癌 / AMBP / 予後因子 / 転移

Outline of Final Research Achievements

In order to identify novel diagnostic biomarkers for the malignant behavior of oral squamous cell carcinoma (OSCC), we determined the proteomic profiles of several OSCC cell lines and keratinocytes. The protein expression level of α-1-microglobulin/bikunin precursor (AMBP) was found to be significantly lower in the OSCC cell lines than in the keratinocytes. To investigate the biological function of AMBP in OSCC, the cells were transiently transfected with an AMBP overexpression vector; the AMBP-overexpressing cells exhibited a significantly decreased invasion and migration. Immunohistochemistry revealed that the underexpression of AMBP was significantly associated with a high metastatic potential to lymph nodes and a poor overall survival. Thus, the expression of AMBP is an independent predictive factor of nodal metastasis and a prognostic factor of overall survival, and it is involved in both cell invasion and metastasis in lymph nodes in OSCC.

Free Research Field

口腔がん

Academic Significance and Societal Importance of the Research Achievements

口腔がんにおいて，頸部リンパ節転移および遠隔臓器転移は患者の予後に直結する重要な因子である。口腔がんの転移に関連する遺伝子産物は多数報告されているが，未だ一定の見解は得られていない．また，近年，口腔・頭頸部領域においても分子標的治療薬の開発が急速にすすんでおり，ターゲットとなる遺伝子産物の機能解析までが必要とされている．
本研究では，口腔扁平上皮癌においてAMBPが高頻度に低発現を示すこと，AMBPの発現低下が癌の浸潤および転移に関連していることを明らかにした．AMBPの周辺分子をさらに検索することで，AMBPが口腔扁平上皮癌の治療ターゲットとして応用できる可能性が示唆された．