Heparanase-1 and components of the hedgehog signalling pathway are increased in untreated alveolar orbital rhabdomyosarcoma

Clin Exp Ophthalmol. 2014 Mar;42(2):182-9. doi: 10.1111/ceo.12139. Epub 2013 Aug 4.

Abstract

Background: To assess the activities of heparanase-1 and elements of the hedgehog signalling pathway in alveolar orbital rhabdomyosarcoma.

Methods: Specimens (n = 23) were divided into two groups, those from patients with preoperative chemoradiotherapy or untreated patients; six samples of normal extraocular muscle were used as a normal muscle group. The presence of heparanase-1, patched, smoothened and glioma-associated oncogene homologue-1 protein expression was determined in 23 cases of archival paraffin-embedded alveolar orbital rhabdomyosarcoma after immunohistochemistry. RNA was extracted from three groups of paraffin-embedded specimens and messenger RNA expressions of heparanase-1, smoothened and glioma-associated oncogene homologue-1 compared using nested reverse transcriptase polymerase chain reaction and a limiting dilution analysis.

Results: The heparanase-1, patched, smoothened and glioma-associated oncogene homologue-1 protein was expressed in 91.3%, 87.0%, 91.3% and 78.3%, respectively, of the alveolar orbital rhabdomyosarcoma specimens. Untreated rhabdomyosarcoma samples tended to stain intensely, but staining was relatively weak in tissue obtained from the chemoradiotherapy group. The expression levels of heparanase-1, smoothened and glioma-associated oncogene homologue-1 messenger RNA in untreated and chemoradiotherapy groups paralleled that seen with immunology, and there were no significant differences in heparanase-1, smoothened and glioma-associated oncogene homologue-1 messenger RNA levels between the chemoradiotherapy group and the normal muscle group (P > 0.05). However, the messenger RNA in the untreated group were all significantly higher than those in the chemoradiotherapy and normal muscle groups (P < 0.01).

Conclusions: Both heparanase-1 and hedgehog signalling pathway are involved in the pathogenesis of alveolar orbital rhabdomyosarcoma; however, chemotherapy and/or radiotherapy appears to significantly inhibit their upregulation.

Keywords: hedgehog; heparanase-1; orbital rhabdomyosarcoma..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Chemoradiotherapy
  • Child
  • Child, Preschool
  • Female
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Orbital Neoplasms / enzymology*
  • Orbital Neoplasms / therapy
  • Patched Receptors
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhabdomyosarcoma, Alveolar / enzymology*
  • Rhabdomyosarcoma, Alveolar / therapy
  • Signal Transduction*
  • Smoothened Receptor
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • Hedgehog Proteins
  • Patched Receptors
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • heparanase
  • Glucuronidase