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

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 PDGFRbeta expressing glioblastoma cell variants by measuring the mobilization of intracellular Ca(2+) 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.

• Authors: Dietmar Gross, Günther Bernhardt, Armin Buschauer
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 132 Issue 9 Pg. 589-99 (Sep 2006) ISSN: 0171-5216 [Print] Germany
• PMID: 16736141 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Platelet-Derived Growth Factor
• RNA, Messenger
• Protein-Tyrosine Kinases
• Receptors, Platelet-Derived Growth Factor

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Gene Expression Profiling
• Glioblastoma (drug therapy, metabolism)
• Humans
• Platelet-Derived Growth Factor (genetics, metabolism)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• RNA, Messenger (genetics)
• Receptors, Platelet-Derived Growth Factor (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity
• Time Factors
• Tumor Cells, Cultured