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Role of hedgehog signaling in malignant pleural mesothelioma

Yandong Shi1, Ubiratan Moura, Isabelle Opitz

  • 1Laboratory of Molecular Oncology, Clinic and Policlinic of Oncology, Division of Thoracic Surgery, Institute of Surgical Pathology, University Hospital Zürich, Zurich, Switzerland.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 27, 2012
PubMed
Abstract

Insights

Aberrant hedgehog signaling is active in malignant pleural mesothelioma (MPM). Inhibiting this pathway significantly reduces tumor growth, suggesting a promising new therapeutic strategy for MPM patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
  • The hedgehog signaling pathway plays a role in various cancers, but its involvement in MPM is not fully understood.

Purpose of the Study:

  • To investigate the activity and therapeutic potential of the hedgehog signaling pathway in malignant pleural mesothelioma.
  • To assess the expression of key hedgehog signaling components in MPM tumors.

Main Methods:

  • Quantitative PCR and in situ hybridization were used to analyze gene expression in 45 clinical MPM samples.
  • In vitro studies involved primary MPM cultures treated with smoothened (SMO) inhibitors or GLI1 silencing.
  • In vivo efficacy was evaluated using an MPM xenograft mouse model treated with SMO antagonists.

Main Results:

  • MPM tumors showed significantly increased expression of GLI1, sonic hedgehog, and human hedgehog interacting protein compared to normal tissue.
  • SMO inhibitors and GLI1 silencing reduced cell growth and GLI1 expression in MPM cultures.
  • In vivo treatment with the SMO inhibitor HhAntag significantly inhibited tumor growth, decreasing proliferation markers (Ki-67) and YAP levels.

Conclusions:

  • Aberrant hedgehog signaling is confirmed in malignant pleural mesothelioma.
  • Inhibition of the hedgehog signaling pathway demonstrates anti-tumor effects, highlighting its potential as a therapeutic target for MPM.

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