http://www.cnr.it/ontology/cnr/individuo/prodotto/ID45879
Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in Vitro and in Vivo. (Articolo in rivista)
- Type
- Label
- Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in Vitro and in Vivo. (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
- Alternative label
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. (2009)
Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in Vitro and in Vivo.
in Neoplasia (N.Y.N.Y.)
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#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. (literal)
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- *Laboratorio Biologia Vascolare e Terapia Genica,
Centro Cardiologico Monzino, IRCCS, Milano, Italy;
Laboratorio Patologia Vascolare, Istituto Dermopatico
dellImmacolata, IDI-IRCCS, Roma, Italy; Laboratorio
Bioinformatica e Biologia Computazionale, Istituto di
Scienza dellAlimentazione CNR, Avellino, Italy;
§Dipartimento Ematologia, Oncologia e Medicina
Molecolare, Istituto Superiore di Sanità, Roma, Italy;
¶Laboratorio Ingegneria Tessutale e Fisiopatologia Cutanea,
Istituto Dermopatico dellImmacolata, IDI-IRCCS, Roma,
Italy; #Dipartimento Anatomia Umana, Policlinico, Bari, Italy (literal)
- Titolo
- Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in Vitro and in Vivo. (literal)
- 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 arraybased 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. (literal)
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