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

Fingerprint

Melanoma
Skin
Cell Line
Messenger RNA
Proteins
Growth
Real-Time Polymerase Chain Reaction
Intercellular Signaling Peptides and Proteins
Flow Cytometry
Western Blotting
Immunohistochemistry
Cell Proliferation
Carcinoma

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression and functional role of CRIPTO-1 in cutaneous melanoma. / 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.

In: British Journal of Cancer, Vol. 105, No. 7, 27.09.2011, p. 1030-1038.

Research output: Contribution to journalArticle

De Luca, A, Lamura, L, Strizzi, L, Roma, C, D'Antonio, A, Margaryan, N, Pirozzi, G, Hsu, MY, Botti, G, Mari, E, Hendrix, MJC, Salomon, DS & Normanno, N 2011, 'Expression and functional role of CRIPTO-1 in cutaneous melanoma', British Journal of Cancer, vol. 105, no. 7, pp. 1030-1038. https://doi.org/10.1038/bjc.2011.324
De Luca A, Lamura L, Strizzi L, Roma C, D'Antonio A, Margaryan N et al. Expression and functional role of CRIPTO-1 in cutaneous melanoma. British Journal of Cancer. 2011 Sep 27;105(7):1030-1038. https://doi.org/10.1038/bjc.2011.324
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. / Expression and functional role of CRIPTO-1 in cutaneous melanoma. In: British Journal of Cancer. 2011 ; Vol. 105, No. 7. pp. 1030-1038.
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