The human melanoma associated protein melanotransferrin promotes endothelial cell migration and angiogenesis in vivo

Roberta Sala, Wilfred A. Jefferies, B. Brandie Walker, Joseph Yang, Jacqueline Tiong, S. K Alex Law, Mariella F. Carlevaro, Eddy Di Marco, Angelo Vacca, Ranieri Cancedda, Fiorella Descalzi Cancedda, Domenico Ribatti

Research output: Contribution to journalArticle

Abstract

Melanotransferrin is a member of the transferrin family, which is comprised of serum transferrin, lactoferrin and ovotransferrin, and is highly expressed on melanoma cells compared to normal melanocytes. Since melanoma is an higly vascularized tumour that expresses melanotransferrin at high levels, we tested purified recombinant melanotransferrin for its capability to induce angiogenesis in the chick chorioallantoic membrane. Macroscopic and microscopic evaluation of the vascular density demonstrated that melanotransferrin exerts an angiogenic response quantitatively similar to that elicited by fibroblast growth factor-2. Overexpression of vascular endothelial growth factor-receptor-2 was observed in newly formed vessels, suggesting that the angiogenic activity of melanotransferrin may depend on activation of endogenous vascular endothelial growth factor. In addition, when antibodies against vascular endothelial growth factor were included in the assay, the angiogenic response was inhibited by 50%. In a Boyden chamber assay purified recombinant melanotransferrin induced chemotactic migration of vascular cells, which was decreased in the the presence of anti-vascular endothelial growth factor antibodies suggesting an involvement of vascular endothelial growth factor present in endothelial cells also in this assay. However, melanotransferrin was found not to directly bind to integrin αvβ3 or the vascular endothelial growth factor-receptor-2 as assessed in a BIAcore assay. A possible correlation between vascularization occurring during melanoma progression and the expression of melanotransferrin and vascular endothelial growth factor was established by immunolocalization of the two factors in sections of melanoma at different clinical steps of melanoma progression. These latter data strongly imply that melanotransferrin may participate in the vascularization of solid tumours and that inhibition of melanotransferrin could form the basis for intervention in tumours which use this pathway.

Original languageEnglish
Pages (from-to)599-607
Number of pages9
JournalEuropean Journal of Cell Biology
Volume81
Issue number11
Publication statusPublished - Nov 1 2002

Keywords

  • Angiogenesisi
  • Melanoma
  • Melanotransferrin
  • Tumor progression

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

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  • Cite this

    Sala, R., Jefferies, W. A., Walker, B. B., Yang, J., Tiong, J., Law, S. K. A., Carlevaro, M. F., Di Marco, E., Vacca, A., Cancedda, R., Cancedda, F. D., & Ribatti, D. (2002). The human melanoma associated protein melanotransferrin promotes endothelial cell migration and angiogenesis in vivo. European Journal of Cell Biology, 81(11), 599-607.