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Journal of Cancer Research and Clinical Oncology

, Volume 132, Issue 9, pp 589–599 | Cite as

Platelet-derived growth factor receptor independent proliferation of human glioblastoma cells: selective tyrosine kinase inhibitors lack antiproliferative activity

  • Dietmar Gross
  • Günther Bernhardt
  • Armin BuschauerEmail author
Original Paper

Abstract

Purpose: The aim of this study was to investigate the role of platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) in the proliferation of human glioblastoma cells as a prerequisite for a new therapeutic approach to the treatment of malignant brain tumors with selective tyrosine kinase inhibitors such as imatinib. Methods and results: In the human glioblastoma cell lines U-87 MG, U-118 MG and U-373 MG different PDGF and PDGFR mRNAs were detected by RT-PCR, and the expression of the receptor proteins was demonstrated by immunostaining and flow cytometry. Moreover, functional activity of PDGFRs was demonstrated in PDGFRβ expressing glioblastoma cell variants by measuring the mobilization of intracellular Ca2+ upon PDGF-BB stimulation. However, addition of PDGF-BB to the serum-free culture medium had no stimulatory effect on cell proliferation. Furthermore, cell growth in serum-supplemented and serum-free medium was not affected by imatinib, leflunomide and AG-1296 at therapeutically relevant concentrations. Conclusion: Our results suggest that clinical antitumor effects of imatinib on glioblastoma, if any, are not mediated by the PDGFR.

Keywords

Platelet-derived growth factor receptor Human glioblastoma cells Imatinib 

Abbreviations

CML

Chronic myelogenous leukemia

FCS

Fetal calf serum

DMSO

Dimethyl sulfoxide

FITC

Fluorescein isothiocyanate

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PDGF

Platelet-derived growth factor

PDGFR

Platelet-derived growth factor receptor

rhPDGF-BB

Recombinant human PDGF-BB

RT-PCR

Reverse transcription polymerase chain reaction

VEGF

Vascular endothelial growth factor

bFGF

Basic fibroblast growth factor

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Dietmar Gross
    • 1
  • Günther Bernhardt
    • 1
  • Armin Buschauer
    • 1
    Email author
  1. 1.Institute of PharmacyUniversity of RegensburgRegensburgGermany

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