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.


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.


CONCLUSIONS
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.
Halatsch
Marc-E
ME
Department of Neurosurgery, Georg-August-University, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. halatsch@aol.com
Gehrke
Esther
E
Borhani
Farhad A
FA
Efferth
Thomas
T
Werner
Carola
C
Nomikos
Panos
P
Schmidt
Ursula
U
Buchfelder
Michael
M
D000077214:Becaplermin; D002455:Cell Division / Q000502:physiology; D066246:ErbB Receptors / Q000096:biosynthesis*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D066246:ErbB Receptors; D020797:Receptor, Platelet-Derived Growth Factor beta