VEGF-C contributes to head and neck squamous cell carcinoma growth and motility.
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.
Benke
Emily M
EM
Philips Institute of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Ji
Youngmi
Y
Patel
Vyomesh
V
Wang
Huixin
H
Miyazaki
Hiroshi
H
Yeudall
W Andrew
WA
D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D054365:Chemokine CXCL5 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D012313:RNA; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*
D054365:Chemokine CXCL5; D009363:Neoplasm Proteins; D042582:Vascular Endothelial Growth Factor C; D012313:RNA