Expression and functional role of CRIPTO-1 in cutaneous melanoma

A. De Luca, L. Lamura, L. Strizzi, C. Roma, A. D'Antonio, N. Margaryan, G. Pirozzi, M. Y. Hsu, G. Botti, E. Mari, M. J C Hendrix, D. S. Salomon, N. Normanno

Research output: Contribution to journalArticlepeer-review

Abstract

Background: CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of human carcinoma of different histological origin. In this study we addressed the expression and the functional role of CR-1 in cutaneous melanoma. Methods: Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated modified Boyden chambers. Results: Expression of CR-1 protein and/or mRNA was found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21 melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased the invasive ability of melanoma cells that was prevented by treatment with either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530). Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive ability of melanoma cells. Finally, a close correlation was found in melanoma cells between the levels of expression of CR-1 and the effects of saracatinib on cell growth. Conclusion: These data indicate that a significant fraction of cutaneous melanoma expresses CR-1 and that this growth factor is involved in the invasion and proliferation of melanoma cells.

Original languageEnglish
Pages (from-to)1030-1038
Number of pages9
JournalBritish Journal of Cancer
Volume105
Issue number7
DOIs
Publication statusPublished - Sep 27 2011

Keywords

  • CRIPTO-1
  • invasion
  • melanoma
  • saracatinib
  • therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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