Cancer Chemotherapy and Pharmacology

, Volume 54, Issue 1, pp 25–33 | Cite as

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

  • Rieko Katayama
  • Michael K. Huelsmeyer
  • Amanda K. Marr
  • Ilene D. Kurzman
  • Douglas H. Thamm
  • David M. Vail
Original Article

Abstract

Feline vaccine-associated sarcoma (VAS) is a biologically aggressive soft-tissue sarcoma that can develop at sites where inactivated feline vaccines have been administered. We showed that platelet-derived growth factor (PDGF) and its receptor (PDGFR) play a role in the growth of VAS cells. The presence of PDGFR-β was confirmed in each of five VAS cell lines evaluated, one non-vaccine-associated feline fibrosarcoma (FSA) cell line and a feline fibroblast-derived cell line. The PDGF/PDGFR signaling pathway was inhibited in the VAS cell lines and the FSA cell line using the tyrosine kinase inhibitor imatinib mesylate (formerly called STI-571). Imatinib inhibited PDGF-BB-induced autophosphorylation of PDGFR in VAS cells and feline FSA cells in vitro in a dose-dependent manner. Imatinib also significantly inhibited growth of feline VAS tumors in a murine xenograft model. Imatinib reversed the protective effect of PDGF-BB on growth inhibition by doxorubicin and carboplatin. PDGF-BB protected VAS cells from serum starvation and doxorubicin-induced apoptosis but not carboplatin-induced apoptosis, and imatinib eliminated this protection. These observations suggest that imatinib inhibits PDGFR tyrosine kinase activity in feline soft tissue sarcomas in vitro and inhibits tumor growth in a xenograft model.

Keywords

Cat PDGFR STI-571 Tyrosine kinase Gleevec 

Abbreviations

C/10

Complete minimal essential medium supplemented with 10% FBS

CPT

Carboplatin

DOX

Doxorubicin

EGF

Epidermal growth factor

FBS

Fetal bovine serum

FSA

Fibrosarcoma

HGF

Hepatocyte growth factor

IGF-1

Insulin-like growth factor-1

MTS

3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

PDGF

Platelet-derived growth factor

PDGFR

Platelet-derived growth factor receptor

PI

Propidium iodide

VAS

Vaccine-associated sarcoma

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Rieko Katayama
    • 1
  • Michael K. Huelsmeyer
    • 1
  • Amanda K. Marr
    • 1
  • Ilene D. Kurzman
    • 1
    • 2
  • Douglas H. Thamm
    • 1
    • 2
  • David M. Vail
    • 1
    • 2
  1. 1.Department of Medical Sciences, School of Veterinary MedicineUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.The Comprehensive Cancer CenterUniversity of Wisconsin-MadisonMadisonUSA

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