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 journalArticle

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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  • Cite this

    De Luca, A., Lamura, L., Strizzi, L., Roma, C., D'Antonio, A., Margaryan, N., Pirozzi, G., Hsu, M. Y., Botti, G., Mari, E., Hendrix, M. J. C., Salomon, D. S., & Normanno, N. (2011). Expression and functional role of CRIPTO-1 in cutaneous melanoma. British Journal of Cancer, 105(7), 1030-1038. https://doi.org/10.1038/bjc.2011.324