Abstract
Problem
Angiogenesis is increased in head and neck squamous cell carcinoma (HNSCC), and correlates with tumor progression and metastasis. Vascular endothelial growth factor (VEGF) has been shown to be a key regulator of angiogenesis. Microvascular density is known to correlate with metastasis and aggressiveness. PDGF and PDGFR are expressed by many tumor types, including HNSCC. The PDGF/PDGFR-System is believed to play a pivotal role in tumorigenesis. The compound STI571 (Imatinib mesylate, Gleevec) inhibits PDGFR tyrosine kinases. In this study, we seek to determine whether targeting PDGFR signalling in HNSCC cell lines may affect expression and secretion of PDGF as well as VEGF in vitro.
Methods
Established human HNSCC cell lines were incubated with STI571 of different concentrations for 24h and 72h. PDGF and VEGF concentrations were determined by an ELISA technique, and gene expression was analyzed by RTPCR.
Results
In vitro treatment of HNSCC cell lines with STI571 resulted in a significant reduction of expression and secretion of PDGF and VEGF. We also observed a dose related effect for VEGF synthesis.
Conclusion
The results in this study suggest, that inhibition of PDGFR using STI571 might have an antitumor effect mediated in part by inhibition of VEGF-induced angiogenesis in HNSCC. Further studies need to be conducted to improve understanding of the molecular mechanisms.
Significance
Our study indicates that STI571 might play a role in establishing new therapeutic strategies against HNSCC.
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