Differential expression of VEGF121, VEGF165 and VEGF189 in angiomas and squamous cell carcinoma cell lines of the head and neck.

Vascular endothelial growth factor A (VEGF) is one of the major regulators of angiogenesis. It plays an important role during the process of physiological and pathological neovascularization. Variant VEGF isoforms are generated as a result of alternative pre-mRNA splicing. To determine the expression of VEGF isoforms in angioma and head and neck squamous cell carcinoma (HNSCC), both being dependent on pathological neovascularization, we included 11 HNSCC cell lines, 4 hemangiomas and 5 vascular malformations (VMs) in the study. Tonsil mucosa served as normal control. Using reverse transcription polymerase chain reaction (RT-PCR) sequencing, the VEGF isoforms VEGF(189), VEGF(165) and VEGF(121) were regularly detected in all tested samples. VEGF(121) was the most abundant isoform in all tested tissues, whereas VEGF(165) exhibited lower levels, and VEGF(189) only very small amounts of transcript. Interestingly, VMs expressed significantly higher (p=0.0286) amounts of VEGF(121) compared with hemangiomas, which had levels similar to normal control mucosa. HNSCC cell lines demonstrated on-average higher levels of all three isoforms compared with the controls. Consistent with the clinical staging, a trend for VEGF overexpression was observed in tumor cells derived from N+ tumors compared to those derived from N0 tumors. One drawback of this study was the small number of specimens available, particularly since VMs and hemangiomas are relatively rare diseases. Future studies need to follow-up on these observations and further evaluate the potential role of specific VEGF isoforms in the pathogenesis of hemangioma and VM.