EGFR but not PDGFR-beta expression correlates to the antiproliferative effect of growth factor withdrawal in glioblastoma multiforme cell lines.

BACKGROUND

The aim of the current study was to investigate a putative relationship between (i) growth characteristics (proliferation and tumorigenicity) of nine glioblastoma multiforme (GBM) cell lines under different growth-stimulating conditions in vitro and (ii) their basal expression of a panel of growth factor receptors/autocrine cytokines.

MATERIALS AND METHODS

Basal expressions of the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-beta (PDGFR-beta), platelet-derived growth factor-AA (PDGF-AA) and PDGF-BB, tumor growth factor-alpha (TGF-alpha) and TGF-beta as well as tumor necrosis factor-alpha (TNF-alpha) were determined by immunocytochemistry at standard cell culture conditions (10% fetal calf serum [FCS]). Proliferation and tumorigenicity at 10% FCS and relative serum starvation (0.5% FCS) were assessed by using Coulter counting and soft agar cloning, respectively.

RESULTS

The ratio between cell multiplications at 10% and 0.5% FCS over a 10-day period was defined as a measure of growth factor dependence of cellular proliferation. Expression of EGFR (but not of PDGFR-beta) strongly correlated to this ratio (Spearman rank correlation coefficient R = 0.87). No considerable correlations were present among other appropriate pairs of variables with biologically founded putative relationships.

CONCLUSION

Greater expression of EGFR is associated with increased growth factor dependence of cellular proliferation. Our results strengthen the role of EGFR as a rational molecular target of therapeutic intervention in GBM.