Effects of hypoxia and reoxygenation on the expression levels of the urokinase-type plasminogen activator, its inhibitor plasminogen activator inhibitor type-1 and the urokinase-type plasminogen activator receptor in human head and neck tumour cells

Oncol Rep. 2007 May;17(5):1259-68.


One aim during oncological radiation therapy is to induce reoxygenation in hypoxic tumours in order to enhance radiosensitivity and ultimately increase cell death. In squamous cell carcinomas of the head and neck (SCCHN), hypoxia is considered a pivotal physiological modulator for malignant progression, whereby the plasminogen activation system is involved in overlapping functions such as the shaping of the extracellular matrix, cell proliferation and signal transduction. Since little is known about reoxygenation and the plasminogen activation system in SCCHN, three human SCCHN cell lines (BHY, FaDu, and CAL27) and a non-transformed control cell line (VH7) were exposed to hypoxic (<0.5% O2) conditions for up to 72 h and subsequently reoxygenated for 24 h at normoxic conditions. The mRNA expression of the urokinase-type plasminogen activator (uPA), the plasminogen activator inhibitor type-1 (PAI-1) and the urokinase-type plasminogen activator receptor (uPAR) was assessed by means of real-time semi-quantitative RT-PCR, and the protein expression was determined by immunoenzymometric quantification (ELISA). Both hypoxia and reoxygenation induced statistically significant changes in uPA, PAI-1 and uPAR mRNA and protein levels in the various cell lines investigated, showing that oxygen tension is a strong modulator of the plasminogen activation system in vitro. However, no uniform correlation pattern was found between the mRNA and protein levels analysed over all three time-points (24, 48, and 72 h) and oxygen treatment variants (N, H, R) nor according to oxygen treatment conditions over all three time-points. Changes in oxygen tension could therefore be modulating the fragile balance between the various components of the plasminogen activation system in SSCHN ultimately leading to an increased tumour matrix disruption, alterations in cell invasiveness, and the dissemination of tumour cells to distant organs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay / methods
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Oxygen / metabolism*
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / metabolism*


  • PLAUR protein, human
  • Plasminogen Activator Inhibitor 1
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator
  • Oxygen