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
Project/Area Number |
16K11245
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Otorhinolaryngology
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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)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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 / 咽頭癌 / 上皮間葉転換 (EMT) / 幹細胞形質 / E-cadherin / 低酸素誘導因子 (HIF) / 糖代謝能 / 独立予後因子 / 頭頸部癌 / 上皮間葉転換(EMT) / がん幹細胞 / 低酸素誘導因子 / 中咽頭癌 / p16 / 生存分析 / 癌幹細胞 / EMT(上皮間葉転換) / Cox2 / 頸部リンパ節転移 / 予後因子 / 多変量解析 / 頭頸部外科学 |
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.
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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。
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Report
(5 results)
Research Products
(42 results)
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[Journal Article] VEGF-C/Flt-4 axis in tumor cells contributes to the progression of oral squamous cell carcinoma via upregulating VEGF-C itself and contactin-1 in an autocrine manner2018
Author(s)
Shigetomi S, Imanishi Y, Shibata K, Sakai N, Sakamoto K, Fujii R, Habu N, Otsuka K, Sato Y, Watanabe Y, Shimoda M, Kameyama K, Ozawa H, Tomita T, Ogawa K
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Journal Title
American Journal of Cancer Research
Volume: 8
Pages: 2046-2063
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pretreatment monocyte counts and neutrophil counts predict the risk for febrile neutropenia in patients undergoing TPF chemotherapy for head and neck squamous cell carcinoma2018
Author(s)
Shimanuki M, Imanishi Y, Sato Y, Nakahara N, Totsuka D, Sato E, Iguchi S, Sato Y, Soma K, Araki Y, Shigetomi S, Yoshida S, Uno K, Ogawa Y, Tominaga T, Ikari Y, Nagayama J, Endo A, Miura K, Tomioka T, Ozawa H, Ogawa K
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Journal Title
Oncotarget
Volume: 9
Issue: 27
Pages: 18970-18984
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical diagnosis and treatment outcomes for parapharyngeal space schwannomas: A single-institution review of 21 cases2018
Author(s)
Sato Y, Imanishi Y, Tomita T, Ozawa H, Sakamoto K, Fujii R, Shigetomi S, Habu N, Otsuka K, Watanabe Y, Sekimizu M, and Ogawa K
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Journal Title
Head Neck
Volume: 40
Issue: 3
Pages: 569-576
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical outcomes of transoral videolaryngoscopic surgery for hypopharyngeal and supraglottic cancer2017
Author(s)
Imanishi Y, Ozawa H, Sakamoto K, Fujii R, Shigetomi S, Habu N, Otsuka K, Sato Y, Watanabe Y, Sekimizu M, Ito F, Tomita T, and Ogawa K
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Journal Title
BMC Cancer
Volume: 17
Issue: 1
Pages: 445-445
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Outcomes and Prognostic Factors for Salivary Duct Carcinoma: A Multi-Institutional Analysis of 141 Patients2016
Author(s)
Otsuka K, Imanishi Y, Tada Y, Kawakita D, Kano S, Tsukahara K, Shimizu A, Ozawa H, Okami K, Sakai A, Sato Y, Ueki Y, Sato Y, Hanazawa T, Chazono H, Ogawa K, Nagao T.Ann Surg Oncol.
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Journal Title
Ann Surg Oncol.
Volume: 23
Issue: 6
Pages: 2038-2045
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Anti-cancer effects of selective Cox-2 and EP2 inhibition through suppression of EMT and the clinical implications of overexpression of Cox-2 and downregulation of E-cadherin in pharyngeal squamous cell carcinoma2017
Author(s)
Yoshihiro Watanabe, Yorihisa Imanishi, Hiroyuki Ozawa, Kaori Kameyama, Koji Sakamoto, Ryoichi Fujii, Seiji Shigetomi, Noboru Habu, Kuninori Otsuka, Yoichiro Sato, Mariko Sekimizu, Fumihiro Ito, Yuichi Ikari, Shin Saito, and Kaoru Ogawa
Organizer
AACR 2017 Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Expression of stem cell markers Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II tongue squamous cell carcinoma2016
Author(s)
Noboru Habu, Yorihisa Imanishi, Kaori Kameyama, Masayuki Shimoda, Yutaka Tokumaru, Koji Sakamoto, Ryoichi Fujii, Seiji Shigetomi, Kuninori Otsuka, Yoichiro Sato, Yoshihiro Watanabe, Hiroyuki Ozawa, Toshiki Tomita, Masato Fujii, Kaoru Ogawa
Organizer
AACR 2016 Annual Meeting
Place of Presentation
New Orleans, USA (Ernest N. Morial Convention Center)
Year and Date
2016-04-19
Related Report
Int'l Joint Research