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Imatinib mesylate inhibits platelet-derived growth factor activity and increases chemosensitivity in feline

Rieko Katayama1, Michael K Huelsmeyer, Amanda K Marr

  • 1Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, Madison, WI 53706, USA.

Cancer Chemotherapy and Pharmacology
|April 27, 2004
PubMed

Insights

Platelet-derived growth factor (PDGF) and its receptor (PDGFR) drive feline vaccine-associated sarcoma (VAS) growth. The drug imatinib mesylate effectively inhibits this pathway, reducing VAS tumor growth in preclinical models.

Area of Science:

  • Veterinary Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Feline vaccine-associated sarcoma (VAS) is an aggressive soft-tissue cancer linked to inactivated vaccine administration sites.
  • Platelet-derived growth factor (PDGF) and its receptor (PDGFR) signaling are implicated in the proliferation of VAS cells.

Purpose of the Study:

  • To investigate the role of the PDGF/PDGFR pathway in feline VAS.
  • To evaluate the efficacy of the tyrosine kinase inhibitor imatinib mesylate in targeting this pathway in feline soft tissue sarcomas.

Main Methods:

  • Confirmed PDGFR-beta expression in multiple VAS cell lines and a feline fibrosarcoma (FSA) cell line.
  • Utilized imatinib mesylate to inhibit the PDGF/PDGFR signaling pathway in vitro.
  • Assessed imatinib's effect on tumor growth in a murine xenograft model and its interaction with chemotherapy agents.

Main Results:

  • Imatinib mesylate dose-dependently inhibited PDGF-BB-induced PDGFR autophosphorylation in VAS and FSA cells.
  • Significant inhibition of feline VAS tumor growth was observed in the xenograft model.
  • Imatinib reversed PDGF-BB's protective effects against doxorubicin and serum starvation-induced apoptosis, but not carboplatin-induced apoptosis.

Conclusions:

  • Imatinib mesylate effectively inhibits PDGFR tyrosine kinase activity in feline soft tissue sarcomas.
  • Targeting the PDGF/PDGFR pathway with imatinib shows promise for treating feline VAS.
  • Imatinib can overcome certain resistance mechanisms to chemotherapy in feline sarcomas.

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