VEGF-C contributes to head and neck squamous cell carcinoma growth and motility

Emily M. Benke, Youngmi Ji, Vyomesh Patel, Huixin Wang, Hiroshi Miyazaki, W. Andrew Yeudall

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)e19-e24
JournalOral Oncology
Volume46
Issue number4
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

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Keywords

  • Motility
  • Oral cancer
  • Proliferation
  • Squamous cell carcinoma
  • Vascular endothelial cell growth factor

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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