title: Thrombospondin-1 is part of a Slug-independent motility and metastatic program in cutaneous melanoma, in association with VEGFR-1 and FGF-2.
abstract: 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.
authors.affiliation: Tumor Angiogenesis Unit, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Borsotti
authors.forename: Carmen
authors.initials: C
authors.lastname: Ghilardi
authors.forename: Paola
authors.initials: P
authors.lastname: Ostano
authors.forename: Antonietta
authors.initials: A
authors.lastname: Silini
authors.forename: Romina
authors.initials: R
authors.lastname: Dossi
authors.forename: Denise
authors.initials: D
authors.lastname: Pinessi
authors.forename: Chiara
authors.initials: C
authors.lastname: Foglieni
authors.forename: Maria
authors.initials: M
authors.lastname: Scatolini
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Lacal
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.forename: Davide
authors.initials: D
authors.lastname: Moscatelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Sangalli
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Atri
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giavazzi
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Bani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chiorino
authors.forename: Giulia
authors.initials: G
authors.lastname: Taraboletti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D008168:Lung / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D010641:Phenotype; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D019700:Thrombospondin 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D019700:Thrombospondin 1; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: FGF-2; Melanoma; Slug; VEGFR-1; cell motility; metastasis; thrombospondin-1