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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in Vitro and in Vivo.
Anno di pubblicazione: 2009
Autori: Faraone, D., Aguzzi, M.S., Toietta, G., Facchiano, A.M., Facchiano, F., Magenta, A., Martelli, F., Truffa, S., Cesareo, E., Ribatti, D., Capogrossi, M.C., Facchiano, A.
Affiliazioni autori: *Laboratorio Biologia Vascolare e Terapia Genica, Centro Cardiologico Monzino, IRCCS, Milano, Italy; †Laboratorio Patologia Vascolare, Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Roma, Italy; ‡Laboratorio Bioinformatica e Biologia Computazionale, Istituto di Scienza dell’Alimentazione CNR, Avellino, Italy; §Dipartimento Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Roma, Italy; ¶Laboratorio Ingegneria Tessutale e Fisiopatologia Cutanea, Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Roma, Italy; #Dipartimento Anatomia Umana, Policlinico, Bari, Italy
Abstract: Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs) is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-R± may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-R± respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-R±. Proliferation was rescued by PDGF-R± inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-R± mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-R± was found to mediate staurosporine cytotoxicity. A protein array–based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-R± show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/B± and a marked increase of p38³, mitogen-activated protein kinase kinase 3, and signal regulatory protein ±1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-R± reached a significant 70% inhibition of primary melanoma growth (P < .001) and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-R± strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control.
Lingua abstract: inglese
Pagine da: 732
Pagine a: 742
Numero volume: 11
Indicizzato da: PubMed 
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