Basic study aiming at anti-metastatic therapy that targets both cancer stem-like cell property and EMT (epithelial to mesenchymal transition) in head and neck cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Keio University
• Principal Investigator: IMANISHI YORIHISA 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (80255538)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 頭頸部扁平上皮癌 / 転移 / EMT（上皮間葉転換 ） / 幹細胞能 / Flt-4 / VEGF-C / Cox-2 / EP2

Outline of Final Research Achievements

Our study demonstrated the following results: 1) Flt-4-expressing HNSCC cells possess their own VEGF-C/Flt-4 autocrine mechanism that enhances tumor cell proliferation and motility via upregulating the expression of VEGF-C itself and CNTN-1, thereby contributing to cancer progression including lymph node metastasis. 2) In pharyngeal cancer cells, selective inhibition of EP2, as well as that of Cox2, can exert anti-metastatic effects via EMT reversal (i.e., by inducing MET) that attenuates cell proliferation and migration. 3) Selective HIF-1α-inhibition may lead to anti-metastatic effects by suppressing both stemness property and EMT in pharyngeal cancer cells.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌における治療成績向上の最大の障壁はその制御困難な転移にある。本研究の結果は，癌転移と薬剤抵抗性に関わるEMTと幹細胞能を同時誘導する分子機構の一端を明らかにし，その関連分子を指標とする転移リスク評価の有用性，およびそれらを標的とする治療の有効性を示唆するものであり，癌診療に新たな戦略を導く可能性が期待される。