Previous work from our laboratory has demonstrated overexpression of
chemokines in
head and neck cancer and the utility of targeting these
proteins for
tumor therapy in a preclinical model. However, the mechanisms involved are unexplored. Through gene expression analysis, we found that expression of
vascular endothelial growth factor (
VEGF-C) was elevated in HN12 cells expressing high levels of CXCL5. In the present study, we have investigated the contribution of
VEGF-C to
tumor cell growth and motility. RNAi-mediated knockdown of
VEGF-C expression in HN12 cells, which express high levels of CXCL5, resulted in a decrease in proliferation. Conversely, forced expression of
VEGF-C in HN4
tumor cells with low endogenous CXCL5 levels increased cell growth. Suppression of
VEGF-C inhibited migration of HN12 cells. Similarly, HN4 cells showed reduced migration towards
conditioned media collected from HN12 cells with
VEGF-C knockdown compared to controls, while HN4/
VEGF-C conditioned media stimulated cell migration. Moreover,
tumor growth in vivo was markedly reduced when
VEGF-C expression was blocked by
shRNA. Finally, determination of
VEGF-C expression in
squamous carcinoma cell lines revealed universal overexpression compared to normal keratinocytes. These findings support a role for
VEGF-C in head and neck squamous cell
carcinogenesis.