Imatinib Targets PDGF Signaling in Melanoma and Host Smooth Muscle Neighboring Cells

• Type: Article in International Scientific Journal
• Date: 2010

Authors

pirraco, a (Author) Other; coelho, p (Author) Other; rocha, a (Author) Other; costa, r (Author) Other; vasques, l (Author) Other; soares, r (Author) FMUP

Journal

Title: Journal of Cellular Biochemistry

Vol. 111

Pages: 433-441

ISSN: 0730-2312

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-003-2FR

DOI: 10.1002/jcb.22725

Abstract (EN): In previous in vitro studies, we showed that imatinib abrogated platelet-derived growth factor receptor alpha (PDGFR alpha) signaling, disrupting both breast cancer and smooth muscle cells (SMC). PDGF is also a powerful mitogen for neural crest origin cells like melanocytes. The purpose of the present study was to evaluate the effect of imatinib on melanoma growth and in angiogenesis, with emphasis to the involvement in PDGF signaling. B16 melanoma cells incubation with 5 mu M (IC50) imatinib resulted in a significant reduction in cell proliferation and migration. Apoptosis, however, was not significantly affected. Phosphorylated-PDGFR alpha expression was decreased in B16 lysates. In a mouse model of B16 melanoma, intraperitoneal administration of imatinib at early day light significantly decreased tumor growth. These findings were corroborated by a highly significant reduction in cell proliferation and increase in apoptosis in melanoma tumors. This was accompanied by a decrease in microvessel density and in the number of SMC-presenting vessels. Imatinib further inhibited PDGFRa expression and activity, as confirmed by the down-regulation of downstream Erk signaling pathway. Altogether, this study demonstrates that besides targeting tumor cells, imatinib also prevents vascular integrity. The current study provides evidence that the paracrine crosstalk between tumor cells and host neighboring cells is crucial for the elucidation of imatinib effects. In addition, the fact that this molecule targets vascular support cells further enlarges its therapeutic purpose to a wide range of vasculoproliferative pathologies. J. Cell. Biochem. 111: 433-441, 2010. (C) 2010 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9