VEGF-C contributes to head and neck squamous cell carcinoma growth and motility
Received 24 November 2009; received in revised form 11 February 2010; accepted 12 February 2010. published online 15 March 2010.
Abstract
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.
aPhilips Institute of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA
bDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA
cMassey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
dClinical and Experimental Orthopedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
eOral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA
Corresponding author. Address: Philips Institute of Oral and Craniofacial Molecular Biology, VCU School of Dentistry, 521 North 11th Street, P.O. Box 980566, Richmond, VA 23298-0566, USA. Tel.: +1 804 828 6415; fax: +1 804 828 0150.
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