Molecular basis for the involvement of thymidine phosphorylase in cancer invasion

Int J Mol Med. 2006 Jun;17(6):1085-91.

Abstract

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), has been implicated in bladder cancer angiogenesis and invasion. However, the molecular basis of its role in invasion remains unclear. We investigated the expression of TP and 10 invasion-related genes in bladder cancers from 72 randomly selected patients by real-time two-step RT-PCR assay. We found that the expression levels of TP, MMP-9, uPA, and MMP-2 were significantly higher in invasive tumors than those in superficial tumors. Also, the expression level of TP significantly correlated with that of uPA, MMP-1, MMP-9, PAI-1 and VEGF. KK47/TP cells, bladder cancer cells that overexpress TP, had a higher expression of MMP-7 and MMP-9 than KK/CV cells that express lower level of TP in hypoxic condition. PC/TP cells, prostate cancer cells that overexpress TP, also had a higher expression of MMP-1 and MMP-7 than PC/CV cells that express no detectable TP. Taken together these data indicate that TP enhances the invasion of tumor cells through the induction of invasion-related genes.

MeSH terms

  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Neoplasm
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Neoplasm Invasiveness / genetics*
  • Plasminogen Activator Inhibitor 1 / genetics
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Thymidine Phosphorylase / genetics*
  • Transcriptional Activation*
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology*
  • Urokinase-Type Plasminogen Activator / genetics

Substances

  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Thymidine Phosphorylase
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9