Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells

J. Lawrence, C. Saba, R. Gogal, O. Lamberth, M. L. Vandenplas, D. J. Hurley, P. Dubreuil, O. Hermine, K. Dobbin, M. Turek

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18 Scopus citations

Abstract

Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalVeterinary and Comparative Oncology
Volume10
Issue number2
DOIs
StatePublished - Jun 1 2012

Keywords

  • Cat
  • Injection-site sarcoma
  • Masitinib
  • Platelet-derived growth factor receptor
  • Tyrosine kinase inhibitor
  • Vaccine-associated sarcoma

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    Lawrence, J., Saba, C., Gogal, R., Lamberth, O., Vandenplas, M. L., Hurley, D. J., Dubreuil, P., Hermine, O., Dobbin, K., & Turek, M. (2012). Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells. Veterinary and Comparative Oncology, 10(2), 143-154. https://doi.org/10.1111/j.1476-5829.2011.00291.x