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.