Elucidation of the mechanism of invadopodia in invasion and metastasis of oral squamous cell carcinoma

• Project/Area Number: 26463038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kanazawa University
• Principal Investigator: Kato Koroku 金沢大学, 附属病院, 講師 (30444201)
• Co-Investigator(Kenkyū-buntansha): 吉澤 邦夫 山梨大学, 大学院総合研究部, 講師 (60452108)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 口腔扁平上皮癌 / Invadopodia / Tks5 / MT1-MMP / 浸潤能 / 遊走能 / 予後 / CAF / ET axis / 浸潤 / 遊走 / 口腔がん / 浸潤突起 / 浸潤・転移 / Caveolin-1 / 接着

Outline of Final Research Achievements

Co-culture with NOF or CAF significantly increased the migration and invasion of both the low-invasive H357 and high-invasive SCC4 cells . The expression level of both Tks5 and MT1-MMP protein and the number of expression spots of Tks5 was significantly increased by culture with NOF-CM or CAF-CM compared with culture with SFM in both H357 and SCC4 cells. Moreover, the migrating and invasive abilities of OSCC cells decreased by inhibition of Tks5.
These results were suggested that invadopodia formation is important mechanism for migration and invasion of OSCC cells and it is regulated by interaction between OSCC cells and fibroblast.

Research Products

• [Journal Article] MicroRNA-205-5p suppresses the invasiveness of oral squamous cell carcinoma by inhibiting TIMP-2 expression. (2018)
  • Author(s): Nagai H, Hasegawa S, Uchida F, Terabe T, Ishibashi Kanno N, Kato K, Yamagata K, Sakai S, Kawashiri S, Sato H, Yanagawa T, Bukawa H.
  • Journal Title: International Journal of Oncology Volume: 52 Pages: 841-850
  • DOI: 10.3892/ijo.2018.4260
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment. (2017)
  • Author(s): Hirai M, Kitahara H, Kobayashi Y, Kato K, Bou-Gharios G, Nakamura H, Kawashiri S.
  • Journal Title: Int J Oncol Volume: 50 Issue: 1 Pages: 41-48
  • DOI: 10.3892/ijo.2016.3785
  • NAID: 120005973600
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. (2016)
  • Author(s): Kitahara H, Hirai M, Kato K, Bou-Gharios G, Nakamura H, Kawashiri S.
  • Journal Title: Oncol Rep Volume: 36 Issue: 6 Pages: 3139-3144
  • DOI: 10.3892/or.2016.5189
  • NAID: 120005973603
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition (2016)
  • Author(s): Ito Kimura, Hiroko Kitahara, Kazuhiro Ooi, Koroku Kato, Natsuyo Noguchi, Kunio Yoshizawa, Hiroyuki Nakamura, Shuichi Kawashiri
  • Journal Title: Oncology Letters Volume: 11 Issue: 1 Pages: 201-207
  • DOI: 10.3892/ol.2015.3833
  • NAID: 120005973602
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Loss of EGFR expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition. (2015)
  • Author(s): Kimura I, Kitahara H, Ooi K, Kato K, Noguchi N, Yoshizawa K, Nakamura H, Kawashiri S.
  • Journal Title: Journal of Oral Pathology and Medicine Volume: 48
  • Peer Reviewed
• [Journal Article] Prognostic value of vascular endothelial growth factor A and C in oral squamous cell carcinoma (2014)
  • Author(s): Yanase M., Kato K., Yoshizawa K., Noguchi N., Kitahara H., Nakamura H
  • Journal Title: Journal of Oral pathology and medicine Volume: (in press) Issue: 7 Pages: 43-43
  • DOI: 10.1111/jop.12167
  • Peer Reviewed / Open Access
• [Presentation] 口腔扁平上皮癌細胞のInvadopodia形成と癌関連線維芽細胞（CAF）との関連 (2017)
  • Author(s): 加藤広禄
  • Organizer: 第41回頭頸部癌学会
• [Presentation] Vinculin negative regulates transcription of MT1-MMP through MEK/ERK pathway (2017)
  • Author(s): 吉本泰祐
  • Organizer: 第35回日本口腔腫瘍学会総会・学術大会
• [Presentation] 口腔扁平上皮癌細胞のInvadopodia形成と癌関連線維芽細胞（CAF)との関連 (2016)
  • Author(s): 加藤広禄、宮澤広樹、加藤阿希、平井真理子、吉本泰祐、木村依世、北原寛子、野口夏代、中村博幸、川尻秀一
  • Organizer: 第61回日本口腔外科学会総会・学術集会
  • Place of Presentation: 幕張メッセ（幕張）
  • Year and Date: 2016-11-26
• [Presentation] The regulation of PD-L1 expression at microenvironment of high grade invasive human oral squamous cell carcinoma (2016)
  • Author(s): Hirai M, Kitahara H, Kimura I, Kato K, Bou-Gharios G, Nakamura H, Kawashiri S
  • Organizer: 24th Biennial Congress of the European Association for Cancer Research
  • Place of Presentation: Manchester Central Convention Complex (Manchester)
  • Year and Date: 2016-07-10
  • Int'l Joint Research
• [Presentation] エリブリンのセツキシマブ非感受性口腔癌細胞出の作用検討 (2016)
  • Author(s): 北原寛子、中村博幸、加藤広禄、野口夏代、大井一浩、川尻秀一
  • Organizer: 第40回頭頚部癌学会総会
  • Place of Presentation: ソニックシティ（さいたま）
  • Year and Date: 2016-06-10
• [Presentation] セツキシマブ非感受性口腔癌細胞でのエリブリンの作用検討 (2016)
  • Author(s): 北原寛子、中村博幸、平井真理子、加藤広禄、川尻秀一
  • Organizer: 第70回日本口腔科学会総会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2016-04-17
• [Presentation] 口腔扁平上皮癌におけるBevacizumabの抗腫瘍効果の実験的検討 (2014)
  • Author(s): 平井真理子、野口夏代、加藤広禄、北原寛子、木村依世、中村博幸、川尻秀一
  • Organizer: 第59回日本口腔外科学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
  • Year and Date: 2014-10-18
• [Presentation] 口腔扁平上皮癌におけるCaveolin-1発現の臨床的意義 (2014)
  • Author(s): 加藤広禄、川尻秀一
  • Organizer: 第23回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール（金沢）
  • Year and Date: 2014-07-10
• [Presentation] 口腔扁平上皮がん浸潤様式４D型におけるがん悪性化に関わる各タンパク発現についての検討 (2014)
  • Author(s): 吉澤邦夫、能崎晋一、柳瀬瑞希、木村依世、北原寛子、野口夏代、加藤広禄、中村博幸、川尻秀一
  • Organizer: 第38回日本頭頸部癌学会総会
  • Place of Presentation: 東京ファッションタウンビル（東京）
  • Year and Date: 2014-06-12
• [Presentation] 口腔扁平上皮癌における病理組織学的分類によるEGFR発現の検討 (2014)
  • Author(s): 木村依世、中村博幸、加藤広禄、平井真理子、柳瀬瑞希、川尻秀一
  • Organizer: 第68回日本口腔科学会学術集会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2014-05-09