Thrombospondin‐1 is part of a Slug‐independent motility and metastatic program in cutaneous melanoma,in association with VEGFR‐1 and FGF‐2 |
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| Authors: | Patrizia Borsotti Carmen Ghilardi Paola Ostano Antonietta Silini Romina Dossi Denise Pinessi Chiara Foglieni Maria Scatolini Pedro M Lacal Raffaele Ferrari Davide Moscatelli Fabio Sangalli Stefania D'Atri Raffaella Giavazzi Maria Rosa Bani Giovanna Chiorino Giulia Taraboletti |
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| Affiliation: | 1. Tumor Angiogenesis Unit, Department of Oncology, IRCCS ‐ Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy;2. Laboratory of Biology and Therapy of Metastasis, Department of Oncology, IRCCS ‐ Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;3. Laboratory of Cancer Genomics, Fondo Edo ed Elvo Tempia Valenta, Biella, Italy;4. Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata‐IRCCS, Rome, Italy;5. Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Milan, Italy;6. Department of Biomedical Engineering, IRCCS ‐ Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy |
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| 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. |
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| Keywords: | Melanoma thrombospondin‐1 cell motility Slug VEGFR‐1 FGF‐2 metastasis |
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