EphA2 as a promoter of melanoma tumorigenicity

Naira V. Margaryan, Luigi Strizzi, Daniel E. Abbott, Elisabeth A. Seftor, M. Sambasiva Rao, Mary J.C. Hendrix, Angela R. Hess*

*Corresponding author for this work

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The greatest health threat from malignant melanoma is death due to metastatic disease. Consequently, the identification of markers predictive of metastatic disease is essential for identifying new therapeutic targets. EphA2, a protein tyrosine kinase receptor commonly expressed in epithelial cells, has been found to be overexpressed and constitutively active in melanoma tumor cells having a metastatic phenotype as characterized by increased invasion, proliferation and vasculogenic mimicry (VM). Based on this observation, we hypothesized that increased expression of EphA2 by melanoma tumor cells could promote these characteristics of a metastatic phenotype in addition to promoting tumorigenicity as a whole. We analyzed a panel of human melanoma tumor cell lines derived from patient tissues classified as primary (either radial growth phase or vertical growth phase) and/or metastatic for the expression of EphA2 and found a correlation between increased EphA2 expression and metastatic potential. Experiments using the most metastatic of the human melanoma cell lines demonstrated that downregulation of EphA2 results in a significant decrease in invasion, proliferation, clonogenicity and VM in vitro, in addition to suppressed tumorigenicity in an orthotopic mouse model. Lastly, utilization of a human phospho-kinase array revealed increased phosphorylation of several different protein kinases involved in mediating various aspects of cellular proliferation. To the best of our knowledge these results provide the first direct in vivo evidence demonstrating a role for EphA2 in promoting melanoma tumorigenicity and suggest EphA2 as a significant molecular target for the therapeutic intervention of malignant melanoma.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalCancer Biology and Therapy
Volume8
Issue number3
StatePublished - Feb 2009

Keywords

  • Cellular proliferation
  • Epha2
  • Melanoma
  • Metastasis
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Margaryan, N. V., Strizzi, L., Abbott, D. E., Seftor, E. A., Sambasiva Rao, M., Hendrix, M. J. C., & Hess, A. R. (2009). EphA2 as a promoter of melanoma tumorigenicity. Cancer Biology and Therapy, 8(3), 279-288.