Role of Neuropeptide Signals Induced Metastasis of Hypopharyngeal Cancer

2010 Fiscal Year Final Research Report

• Project/Area Number: 20592011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Chiba University
• Principal Investigator: HANAZAWA Toyoyuki Chiba University, 大学院・医学研究院, 准教授 (90272327)
• Co-Investigator(Kenkyū-buntansha): 関 直彦 千葉大学, 大学院・医学研究院, 准教授 (50345013)
• Project Period (FY): 2008 – 2010
• Keywords: 下咽頭癌 / ゲノム / 神経ペプチド / マイクロRNA / 遺伝子解析

Research Abstract

Distant metastasis is a major factor associated with poor prognosis in hypopharyngeal squamous cell carcinomas (HSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. We narrowed our focus to the analysis of the neurotensin (NT) and neurotensin receptor (NTR) oncogenic signal pathways. In HSCC cells, which expressed NTR, a NT agonist promoted cellular invasion, migration and induction of several mRNAs, such as interleukin 8 and matrix metalloproteinase 1 transcripts. Our findings suggest a critical role for the NT and NTR oncogenic pathways in invasion and migration of HSCC cells during the metastatic process. Our study raises the possibility that NT and NTR could be a useful predictive marker of poor prognosis in patients with HSCC.

Research Products

• [Journal Article] Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. (2011)
  • Author(s): Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Fujimura L, Yoshino H, Kawakami K, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N
  • Journal Title: Int J Oncol. 38(1) Pages: 209-217
• [Journal Article] miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC). (2010)
  • Author(s): Kikkawa N, Hanazawa T, Fujimura L, Nohata N, Suzuki H, Chazono H, Sakurai D, Horiguchi S, Okamoto Y, Seki N.
  • Journal Title: Br J Cancer. 7;103(6) Pages: 877-884
• [Journal Article] マイクロRNA(miR-145、miR-133a・b)の頭頸部扁平上皮癌における増殖・浸潤抑制機能と標的遺伝子の同定 (2010)
  • Author(s): 花澤豊行, 吉川直子, 野畑二次郎, 堅田浩司, ムラディル・ムラリフ, 鈴木誉, 佐々木慶太, 茶薗英明, 堀口茂俊, 岡本美孝, 関直彦
  • Journal Title: 頭頸部癌 36(1) Pages: 1-8
• [Journal Article] The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma. (2009)
  • Author(s): Sugimoto T, Seki N, Shimizu S, Kikkawa N, Tsukada J, Shimada H, Sasaki K, Hanazawa T, Okamoto Y, Hata A
  • Journal Title: Genes Chromosomes Cancer. 48(2) Pages: 132-142
• [Journal Article] Identification of a novel therapeutic target for head and neck squamous cell carcinomas : A role for the neurotensin-neurotensin receptor 1 oncogenic signaling pathway. (2008)
  • Author(s): Shimizu S, Tsukada J, Sugimoto T, Kikkawa N, Sasaki K, Chazono H, Hanazawa T, Okamoto Y, Seki N
  • Journal Title: Int J Cancer. 15;123(8) Pages: 1816-1823
• [Presentation] miR-133aas a tumor suppressive microRNA targeting multiple oncogenes in head neck squamous cell carcinoma. (2011)
  • Author(s): Nohata N.
  • Organizer: AACR102nd
  • Place of Presentation: Orland
  • Year and Date: 2011-04-03
• [Presentation] miR-15a as potential therapeutic molecule for head and neck squamous cell carcinoma (HNSCC). (2010)
  • Author(s): 花澤豊行
  • Organizer: AACR101st
  • Place of Presentation: Washington DC
  • Year and Date: 2010-04-19
• [Presentation] 下咽頭SCCの遺伝子発現プロファイルによるmicroRNA発現多様性の同定 (2009)
  • Author(s): 吉川直子
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] ニューロテンシンシグナルによる頭頸部扁平上皮癌転移・浸潤機構の解明 (2008)
  • Author(s): 花澤豊行
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] ゲノム解析に基づく頭頸部扁平上皮癌・分子標的の探索(1)ガラニンレセプターを介するシグナル伝達機構の解明 (2008)
  • Author(s): 花澤豊行
  • Organizer: 第32回日本頭頸部癌学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-13