Anti-metastatic therapy that simultaneously leads to both loss of cancer stem-like cell property and MET (mesenchymal to epithelial transition) in head and neck cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09876
• 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: International University of Health and Welfare (2020-2022); Keio University (2019)
• Principal Investigator: Imanishi Yorihisa 国際医療福祉大学, 医学部, 教授 (80255538)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 頭頸部癌 / 咽頭扁平上皮癌 / 転移 / 頸部リンパ節 / EMT（上皮間葉転換） / 癌幹細胞特性 / Cox-2 / EP2

Outline of Final Research Achievements

1) In pharyngeal squamous cell carcinoma (PSCC) cells, selective inhibition of Cox2 and its downstream EP2 (PGE2 receptor) showed antitumor effects by suppressing cell proliferation and migration via MET-induction (EMT-reversal) through downregulation of various EMT-TFs. Histopathological analysis of hypopharyngeal carcinoma specimens suggested a profound involvement of EMT, characterized by decreased E-cadherin expression and increased Cox2 expression, in cervical lymph node metastasis.
2) Selective Cox2 and EP2 inhibition of PSCC cells attenuates anchorage-independent cell proliferative ability by down-regulating several CSC-related molecules such as Oct3/4 and Nanog, thereby enhancing chemosensitivity to docetaxel. Immunohistochemical analysis of oro-hypopharyngeal carcinoma specimens before and after induction chemotherapy displayed a significant inverse correlation between pre-treatment Cox2 expression and the histological therapeutic effect of induction chemotherapy.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

頭頸部扁平上皮癌における治療成績向上の最大の障壁は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の双方に関わるEMT（上皮間葉転換）と癌幹細胞能を同時に誘導する分子機構の一端を明らかにすることにより，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，癌診療の新たな戦略の実現可能性が期待される。