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Hypoxia negatively regulates heparan sulfatase 2 expression in renal cancer cell lines

Ashwani Khurana1, Han W Tun, Laura Marlow

  • 1Department of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Molecular Carcinogenesis
|July 9, 2011
PubMed

Insights

The von Hippel-Lindau (VHL) tumor suppressor gene inactivation in clear cell renal cell carcinoma (ccRCC) upregulates heparan sulfatase 2 (HSulf-2). HSulf-2 then attenuates growth factor signaling, revealing a new regulatory mechanism in ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is a key event in clear cell renal cell carcinoma (ccRCC) pathogenesis.
  • VHL loss promotes pro-tumorigenic signaling pathways, including those involving growth factors like bFGF2, SDF-1α, and HGF.

Purpose of the Study:

  • To identify novel genes regulated by VHL inactivation in ccRCC.
  • To investigate the role of identified genes in modulating growth factor signaling and tumor progression.

Main Methods:

  • Gene expression analysis to identify VHL-inducible genes.
  • Western blotting and quantitative PCR to assess protein and gene expression levels.
  • Cell migration assays and vimentin knockdown experiments.

Main Results:

  • Heparan sulfatase 2 (HSulf-2) was identified as a novel VHL-inducible gene.
  • HSulf-2 expression is restored by VHL-mediated HIF-1 alpha degradation.
  • HSulf-2 attenuates bFGF2 signaling and negatively regulates vimentin expression, thereby inhibiting cell migration.

Conclusions:

  • HSulf-2 represents a novel VHL-regulated gene that suppresses ccRCC progression.
  • HSulf-2 modulates heparan sulfate-mediated growth factor signaling, offering a new therapeutic target for ccRCC.

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