Analysis of epithelial integrity system in tumor invasion and metastasis of oral cancer

2011 Fiscal Year Final Research Report

• Project/Area Number: 21592526
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: HIGASHIKAWA Koichiro 広島大学, 病院, 講師 (80363084)
• Co-Investigator(Kenkyū-buntansha): KAMATA Nobuyuki 広島大学, 大学院・医歯薬学総合研究科, 教授 (70242211) ; TOBIUME Kei 広島大学, 大学院・医歯薬学総合研究科, 准教 (40350037) ; SHIGEISHI Hideo 広島大学, 大学院・医歯薬学総合研究科, 助教 (90397943)
• Co-Investigator(Renkei-kenkyūsha): ONO Shigehiro 広島大学, 大学院・医歯薬学総合研究科, 助教研 (70379882)
• Project Period (FY): 2009 – 2011
• Keywords: 口腔癌 / 上皮間葉移行 / 癌の浸潤・転移 / p^63 / 上皮整合性

Research Abstract

Epithelial-Mesencymal Transition(EMT) is involved in tumor invasion and metastasis of oral squamous cell carcinomas(SCCs). Snail, a transcription factor and EMT inducer, directs transcription of its target genes for the acquisition of EMT in SCC cells. We focused a process of loss of epithelial integrity among SCC cells during the EMT. For the investigation of that, we generated SCC cell pools of forced Snail expression by recombinant virus infection system. Almost the cells displayed constant expression of exogenous Snail, however, a small population of the cells underwent EMT. The cells on culture dish were given the migration area and were escalated into EMT. Immnocytochemistory and immnoblot analyses showed that loss of epithelial integrity and cell-cell contact were the last step of EMT process and the process was accelerated by distinct humoral factors.

Research Products

• [Journal Article] PGE(2) targets squamous cell carcinoma cell with the activated epidermal growth factor receptor family for survival against 5-fluorouracil through NR4A2 induction (2011)
  • Author(s): Shigeishi H, Higashikawa K, Hatano H, Okui G, Tanaka F, Tran TT, Rizqiawan A, Ono S, Tobiume K, Kamata N
  • Journal Title: CancerLett Volume: 307(2) Pages: 227-36
  • Peer Reviewed
• [Journal Article] Lymphangiogenesis and metastasis : Role of tumor-inducedlymphatic vessel activation in extramammary Paget' s disease (2009)
  • Author(s): Hirakawa S, Detmar M, Kerjaschki D, Nagamatsu S, Matsuo K, Tanemura A, Kamata N, Higashikawa K, Okazaki H, Kameda K, Nishida-Fukuda H, Mori H, Hanakawa Y, Sayama K, Shirakata Y, Tohyama M, Tokumaru S, Katayama I, Hashimoto K
  • Journal Title: Am JPathol Volume: 175(5) Pages: 2235-48
  • Peer Reviewed
• [Journal Article] Overexpression of the receptor for hyaluronan-mediated motility, correlates with expression of microtubule-associated protein in human oral squamous cell carcinomas (2009)
  • Author(s): Shigeishi H, Fujimoto S, Hiraoka M, OnoS, Taki M, Ohta K, Higashikawa K, Kamata N
  • Journal Title: Int J Oncol Volume: 34(6) Pages: 1565-1571
  • Peer Reviewed
• [Journal Article] DeltaNp63alpha-dependent expression of Id-3 distinctively suppresses the invasiveness of human squamous cell carcinoma (2009)
  • Author(s): Higashikawa K, Yoneda S, Tobiume K, Saitoh M, Taki M, Mitani Y, Shigeishi H, Ono S, Kamata N
  • Journal Title: Int J Cancer Volume: 124(12) Pages: 2837-2844
  • Peer Reviewed
• [Presentation] 癌細胞の浸潤・転移 (2011)
  • Author(s): 東川晃一郎
  • Organizer: 口腔癌治療における遺伝子診断の役割
  • Place of Presentation: 東京都
  • Year and Date: 2011-04-21
• [Presentation] Epithelial Mesennchymal Transitionと腫瘍の転移・浸潤 (2009)
  • Author(s): 鎌田伸之, 東川晃一郎
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-03