Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Osaka University
• Principal Investigator: OUE Takaharu 大阪大学, 医学(系)研究科(研究院), 講師 (50314315)
• Co-Investigator(Kenkyū-buntansha): FUKUZAWA Masahiro 大阪大学, 医学部, 名誉教授 (60165272) ; UEHARA Shuichiro 大阪大学, 医学部, 助教 (00448060)
• Project Period (FY): 2011 – 2013
• Keywords: ヘッジホグ / Gli-1 / 阻害剤 / cyclopamine / forskolin / 細胞増殖 / 横紋筋肉腫 / 分子標的治療

Research Abstract

The objective of this study was to determine whether Hedgehog signaling plays a role in the invasion of RMS. Two kinds of specific Hh signaling inhibitors, cyclopamine and forskolin, were used to suppress activated Hh signals in three RMS cell lines. The effects of the Hh signaling inhibitors on tumor cell invasion and motility were investigated using Matrigel Invasion assays and wound closure assays, respectively. The number of invaded cells in the Matrigel chambers was significantly decreased. The wound closure assays revealed that a blockade of the Hh signaling pathway impairs RMS cell motility. Both the invasive capacity and motility of RMS cells are significantly suppressed by Hh signaling inhibitors, demonstrating that the Hh pathway plays an important role in the invasion of RMS. Hh inhibitors may provide a new paradigm for the treatment of RMS.

Research Products

• [Journal Article] Bilateral Wilms tumors treated according to the Japan Wilms Tumor Study Group protocol (2014)
  • Author(s): Oue T, Koshinaga T, Okita H, Kaneko Y, Hinotsu S, Fukuzawa M
  • Journal Title: Pediatr Blood Cancer Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells (2013)
  • Author(s): Oue T, Uehara S, Yamanaka H, Nomura M, Usui N
  • Journal Title: Pediatr Surg Int Volume: 29 Pages: 1153-8
  • Peer Reviewed
• [Journal Article] Low serum concentrations of anti-Mullerian hormone are common in 53 female childhood cancer survivors (2013)
  • Author(s): Miyoshi Y, Ohta H, Namba N, Tachibana M, Miyamura T, Miyashita E, Hashii Y, Oue T, Isobe A, Tsutsui T, Kimura T, Ozono K
  • Journal Title: Horm Res Paediatr Volume: 79 Pages: 17-21
  • Peer Reviewed
• [Journal Article] 頬部横紋筋肉腫に対する集学的治療後4年で発生した耳下腺悪性腫瘍の1例 (2013)
  • Author(s): 上原秀一郎, 太田秀明, 山本佳史, 橋井佳子, 大植孝治, 福澤正洋
  • Journal Title: 日本小児血液・がん学会雑誌 Volume: 50 Pages: 232-236
  • Peer Reviewed
• [Journal Article] Expression of Wilms tumor 1 gene in a variety of pediatric tumors (2011)
  • Author(s): Oue T, Uehara S, Yamanaka H, Takama Y, Oji Y, Fukuzawa M
  • Journal Title: J Pediatr Surg Volume: 46 Pages: 2233-8
  • Peer Reviewed
• [Journal Article] The role of WT1 gene in neuroblastoma (2011)
  • Author(s): Wang J, Oue T, Uehara S, Yamanaka H, Oji Y, Fukuzawa M
  • Journal Title: J Pediatr Surg Volume: 46 Pages: 326-31
  • Peer Reviewed
• [Journal Article] Hedgehog signal inhibitor forskolin suppresses cell proliferation and tumor growth of human rhabdomyosarcoma xenograft (2011)
  • Author(s): Yamanaka H, Oue T, Uehara S, Fukuzawa M
  • Journal Title: J Pediatr Surg Volume: 46 Pages: 320-5
  • Peer Reviewed
• [Presentation] 無血清培養から抽出した胞巣型横紋筋肉腫幹細胞の生物学的特徴 (2013)
  • Author(s): 上原秀一郎, 中畠賢吾, 川津美代子, 大植孝治, 臼井規朗
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20131129-1201
• [Presentation] 頬部横紋筋肉腫に対する集学的治療後4年で発生した耳下腺悪性腫瘍の1例 (2013)
  • Author(s): 上原秀一郎, 太田秀明, 山本佳史, 橋井佳子, 大植孝治, 福澤正洋
  • Organizer: 第55回日本小児血液・がん学会
  • Place of Presentation: 福岡
  • Year and Date: 20131129-1201
• [Presentation] 横紋筋肉腫細胞の浸潤能におけるHedgehogシグナル系の関与 (2013)
  • Author(s): 大植孝治, 上原秀一郎, 野村元成, 上野豪久, 奈良啓吾, 曹英樹, 臼井規朗, 山中宏晃, 福澤正洋
  • Organizer: 第50回日本小児外科学会
  • Place of Presentation: 東京
  • Year and Date: 20130530-0601
• [Presentation] 無血清培養より抽出した胞巣型横紋筋肉腫幹細胞様細胞の生物学的特徴 (2013)
  • Author(s): 上原秀一郎, 川津美代子, 野村元成, 奈良啓吾, 上野豪久, 曹英樹, 大植孝治, 臼井規朗
  • Organizer: 第113回日本外科学会
  • Place of Presentation: 福岡
  • Year and Date: 20130411-13
• [Presentation] Bilateral Wilms'tumors treated according to the Japan Wilms Tumor Study Group protocol (2013)
  • Author(s): Oue T, Fukuzawa M, Okita H, HorieH, Saito M, Nozaki M, Chin M, Nakadate N, Hinotsu S, Koshinaga T, Kaneko Y, Tanaka Y
  • Organizer: 45^<th> Congress of the International Society of Paediatric Oncology
  • Place of Presentation: Hong Kong, China
  • Year and Date: 20130000
• [Presentation] Novel strategy for neuroblastoma with the combination of 13-cis-retinoic acid and inactivated Sendai virus particle (2013)
  • Author(s): Nomura M, Uehara S, Oue T, Usui N
  • Organizer: 14^<th> Congress of the European Paediatric Surgeons' Association
  • Place of Presentation: Leipzig, Germany
  • Year and Date: 20130000
• [Presentation] 小児悪性固形腫瘍に対する新たな治療標的分子の検討 (2012)
  • Author(s): 大植孝治, 奈良啓吾, 山中宏晃, 野村元成, 上原秀一郎, 福澤正洋
  • Organizer: 第112回日本外科学会
  • Place of Presentation: 幕張
  • Year and Date: 20120412-14
• [Presentation] Problema of Childhood Cancer Survivers in Pediatric Surgical Clinic (2012)
  • Author(s): OueT, Uehara S, Fukuzawa M, Miyoshi Y, Ohta H, Hashii Y
  • Organizer: 44^<th> Congress of the International Society of Paediatric Oncology
  • Place of Presentation: London, UK
  • Year and Date: 20120000
• [Presentation] Hedgehog Signal Inhibitors Supress the Invasion of Human Rhabdomyosarcoma Cells (2012)
  • Author(s): OueT, Uehara S, Yamanaka H, Takama Y, Fukuzawa M
  • Organizer: 59^<th> Cogress of the British Association of Paediatric Surgeons
  • Place of Presentation: Rome, Italy
  • Year and Date: 20120000
• [Presentation] The expression of survivin and its increased expression after chemotherapy in hepatoblastoma (2012)
  • Author(s): Uehara S, Kawatsu M, Oue T, Fukuzawa M
  • Organizer: XXV International Symposium on Paediatric Surgical Research
  • Place of Presentation: London, UK
  • Year and Date: 20120000
• [Presentation] The use of tissue expanders to prevent the side effect of preoperative radiotherapy in pediatric malignant pelvic tumors (2012)
  • Author(s): Uehara S, Oue T, Takenaka S, Hashimoto N, Adachi K, Matsumura R, Yoshida H, Hashii Y, Fukuzawa M
  • Organizer: 44^<th> Congress of the International Society of Paediatric Oncology
  • Place of Presentation: London, UK
  • Year and Date: 20120000
• [Presentation] 横紋筋肉腫細胞株に対するヘッジホッグシグナル伝達経路阻害剤フォルスコリンの浸潤抑制効果の検討 (2011)
  • Author(s): 山中宏晃, 大植孝治, 上原秀一郎, 福澤正洋
  • Organizer: 第53回日本小児血液がん学会
  • Place of Presentation: 前橋
  • Year and Date: 20111125-27
• [Presentation] 当院における横紋筋肉腫22症例の臨床病理学的検討特に再発・転移症例と大量化学療法について (2011)
  • Author(s): 上原秀一郎, 野村元成, 山中宏晃, 大植孝治, 橋井佳子, 太田秀明, 福澤正洋
  • Organizer: 第48回日本小児外科学会
  • Place of Presentation: 東京
  • Year and Date: 20110720-22
• [Book] 小児外科診療ハンドブック(福澤正洋監修)超音波検査, 腫瘍生検, 肝芽腫, 腎芽腫, 横紋筋肉腫, 精巣腫瘍 (2014)
  • Author(s): 大植孝治
  • Total Pages: 58-6, 133-137, 438-445, 446-452, 543-462, 476-481
  • Publisher: 医薬ジャーナル社
• [Book] スタンダード小児外科手術(田口智章、岩中督監修)腫瘍生検、縦隔腫瘍の手術 (2013)
  • Author(s): 大植孝治
  • Total Pages: 58-61, 111-113
  • Publisher: メジカルビュー社
• [Book] 系統小児外科学第3版(福澤正洋、中村哲郎、窪田昭男編),病理組織検査法, 分子標的治療, 再生医療, 腎芽腫, 肝腫瘍, 横紋筋肉腫, 膵腫瘍, 悪性リンパ腫 (2013)
  • Author(s): 大植孝治
  • Total Pages: 72-74, 327-330, 331-336, 712-718, 719-729, 730-736, 743-746, 754-756
  • Publisher: 永井書店