PAI-1 levels predict response to fractionated irradiation in 10 human squamous cell carcinoma lines of the head and neck

Bayer, Christine; Schilling, Daniela; Hoetzel, Joerg; Egermann, Hannes Peter; Zips, Daniel; Yaromina, Ala; Geurts-Moespot, Anneke; Sprague, Lisa Deborah; Sweep, Fred; Baumann, Michael; Molls, Michael; Adam, Markus

doi:10.1016/j.radonc.2007.11.011

« Previous Next »Radiotherapy & Oncology
Volume 86, Issue 3 , Pages 361-368, March 2008

PAI-1 levels predict response to fractionated irradiation in 10 human squamous cell carcinoma lines of the head and neck

Christine Bayer
- Department of Radiation Oncology, Technical University of Munich, Munich, Germany
- Corresponding author. Christine Bayer, Department of Radiation Oncology, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.
Daniela Schilling
- Department of Radiation Oncology, Technical University of Munich, Munich, Germany
Joerg Hoetzel
- Department of Radiation Oncology, Technical University of Munich, Munich, Germany
Hannes Peter Egermann
- Department of Radiation Oncology, Technical University of Munich, Munich, Germany
Daniel Zips
- Department of Radiation Oncology, Carl Gustav Carus University of Technology, Dresden, Germany
Ala Yaromina
- Department of Radiation Oncology, Carl Gustav Carus University of Technology, Dresden, Germany
Anneke Geurts-Moespot
- Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Lisa Deborah Sprague
- Institute of Molekulare Pathogenese, Friedrich-Loeffler-Institut, Bundesforschungsinstitut for Tiergesundheit, Jena, Germany
Fred Sweep
- Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Michael Baumann
- Department of Radiation Oncology, Carl Gustav Carus University of Technology, Dresden, Germany
Michael Molls
- Department of Radiation Oncology, Technical University of Munich, Munich, Germany
Markus Adam
- Radiotherapy Practice, Weilheim, Germany

Received 20 August 2007; received in revised form 9 November 2007; accepted 9 November 2007. published online 12 December 2007.

Abstract

Background and purpose

To investigate the relationships between hypoxia, VEGF and components of the plasminogen activation system (PAS) and to determine their influence on local tumour control after fractionated radiotherapy.

Material and methods

Ten cell lines derived from human squamous cell carcinomas of the head and neck (SCCHN) were investigated in vitro and used to generate xenograft tumours. The pimonidazole hypoxic fraction in the total tumour area (pHF_tot) was used to measure hypoxia in pre-treatment tumours and the local tumour control (TCD₅₀) was used as the functional endpoint in vivo. For in vitro experiments, cells were cultured for 24h under either normoxic or mild hypoxic (∼0.66% O₂) conditions. VEGF, PAI-1 and uPA antigen levels were determined by ELISA and uPA activity by an activity assay kit.

Results

Of all the factors investigated, only PAI-1 expression correlated with TCD₅₀ (r=0.80, p=0.010) and was significantly higher (p=0.001) in more hypoxic than in less hypoxic tumours. Accordingly, PAI-1 secretion was significantly induced (2.4×) by in vitro hypoxia.

Conclusions

These results suggest that pre-treatment PAI-1 levels are higher in more hypoxic tumours and can predict the response to fractionated irradiation in SCCHN.

Keywords: Hypoxia, VEGF, Plasminogen activation system (PAS), Squamous cell carcinomas, Human tumour xenograft, Local tumour control