gms | German Medical Science

Introduction: In this study we examined the influence of tyrosine kinase inhibitor STI571 on migratory behavior of human glioma cells. STI571 which primarily inhibits Bcr-Abl, c-Kit and PDGF tyrosine kinase receptor acts by disruption of the ligand receptor autocrine loops for PDGF factor that are a pervasive feature of malignant astrocytoma.

Methods: Using RT-PCR, immunocytochemistry and flow-cytometry, we provided evidence of PDGF a/b receptor DNA presence and its cell surface expression in three human glioblastoma multiforme (GBM) cell lines and one fibrillary astrocytoma cell line. Migration rate (MR) was examined by the time-lapse individual cell migration assay (TIM-Assay), allowing continuous observation of cells in a time frame of 24 hours under defined conditions. During the TIM-Assay, each cell line was treated with 0.2, 5 and 20 µM STI571, these concentrations corresponding to the drug level in cerebrospinal fluid and plasma in vivo. Furthermore, cell migration was measured using petri dishes coated with extra-cellular matrix.

Results: All cell lines showed PDGF a/b receptor expression. In most tested cell lines, MR decreased after treatment with STI571. One GBM showed an inherently low MR without STI571 treatment. In the other three cell lines MR was reduced already at the lowest STI571 concentration. For example in one GBM, the initial mean MR was 18 µm/h and decreased to 13 µm/h at 0.2 µM, to 8 µm/h at 5 µM and to 6 µm/h at 20 µM STI571 concentration. Without STI571 MR increased slightly on petri dishes coated with extra-cellular matrix.

Conclusions: PDGF a/b receptor expression could be relevant in determining the MR. Targeting of PDGF signaling pathway by tyrosine kinase inhibitor represents a promising strategy to interfere with the migration activity of glioma cells.