Imatinib targets PDGF signaling in melanoma and host smooth muscle neighboring cells

Ana Pirraco, Pedro Coelho, Ana Rocha, Raquel Costa, Luísa Vasques, Raquel Soares*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

In previous in vitro studies, we showed that imatinib abrogated platelet-derived growth factor receptor a (PDGFRa) 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 μM (IC50) imatinib resulted in a significant reduction in cell proliferation and migration. Apoptosis, however, was not significantly affected. Phosphorylated-PDGFRα 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 PDGFRα 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.

Original languageEnglish
Pages (from-to)433-441
Number of pages9
JournalJournal of Cellular Biochemistry
Volume111
Issue number2
DOIs
Publication statusPublished - 1 Oct 2010
Externally publishedYes

Keywords

  • Angiogenesis
  • Glivec
  • Melanoma
  • Smooth muscle cells

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