Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells.

Purpose: In the treatment of rhabdomyosarcoma (RMS), invasion and metastasis remain the most critical determinants of resectability and survival. The objective of this study was to determine whether Hedgehog (Hh) signaling plays a role in the invasion of RMS.Methods: Two kinds of specific Hh signali...

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Published in:Pediatric Surgery International Vol. 29; no. 11; pp. 1153 - 1159
Main Authors: Oue, Takaharu, Uehara, Shuichiro, Yamanaka, Hiroaki, Nomura, Motonari, Usui, Noriaki
Format: research Journal Article
Published: Springer Nature Nov2013
Online Access:View this record in EBSCOhost
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      dt: Nov2013
      vid: 29
      iid: 11
      pid: 237
      pub: Springer Nature
      place: New York, New York
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        10.1007/s00383-013-3369-6
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        atl: Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells.
      aug:
        au:
          Oue, Takaharu
          Uehara, Shuichiro
          Yamanaka, Hiroaki
          Nomura, Motonari
          Usui, Noriaki
        affil: Division of Pediatric Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan, ooue@pedsurg.med.osaka-u.ac.jp.
      sug:
        subj:
          Terpenes Pharmacodynamics
          Proteins Metabolism
          Neoplasm Invasiveness
          Rhabdomyosarcoma Metabolism
          Alkaloids Pharmacodynamics
          Biological Response Modifiers Pharmacodynamics
          Cell Line, Tumor
          Cell Movement
          Disease Progression
          Proteins Antagonists and Inhibitors
          Human
          Rhabdomyosarcoma Drug Therapy
          Rhabdomyosarcoma Pathology
          Signal Transduction
      ab: Purpose: In the treatment of rhabdomyosarcoma (RMS), invasion and metastasis remain the most critical determinants of resectability and survival. The objective of this study was to determine whether Hedgehog (Hh) signaling plays a role in the invasion of RMS.Methods: 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.Results: The number of invaded cells counted in six random microscopic fields in the Matrigel chambers was significantly decreased by both cyclopamine and forskolin in every RMS cell line. Furthermore, the wound closure assays revealed that a blockade of the Hh signaling pathway by the Hh inhibitors strongly impairs RMS cell motility, as visualized by the delayed closure of the gaps generated in the cultured cell monolayers of the three RMS cell lines.Conclusions: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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