Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 28, Issue 1, Pages -Publisher
WILEY
DOI: 10.1111/pcmr.12319
Keywords
Melanoma; thrombospondin-1; cell motility; Slug; VEGFR-1; FGF-2; metastasis
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Funding
- Associazione Italiana per la Ricerca sul Cancro [AIRC IG-13272]
- Italian Ministry of Health [GR2007, Oncord 25/07]
- Comitato Emme Rouge in Ricordo di Mara Nahum
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Differently from most transformed cells, cutaneous melanoma expresses the pleiotropic factor thrombospondin-1 (TSP-1). Herein, we show that TSP-1 (RNA and protein), undetectable in four cultures of melanocytes and a RGP melanoma, was variously present in 13 cell lines from advanced melanomas or metastases. Moreover, microarray analysis of 55 human lesions showed higher TSP-1 expression in primary melanomas and metastases than in common and dysplastic nevi. In a functional enrichment analysis, the expression of TSP-1 correlated with motility-related genes. Accordingly, TSP-1 production was associated with melanoma cell motility in vitro and lung colonization potential in vivo. VEGF/VEGFR-1 and FGF-2, involved in melanoma progression, regulated TSP-1 production. These factors were coexpressed with TSP-1 and correlated negatively with Slug (SNAI2), a cell migration master gene implicated in melanoma metastasis. We conclude that TSP-1 cooperates with FGF-2 and VEGF/VEGFR-1 in determining melanoma invasion and metastasis, as part of a Slug-independent motility program.
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