Nerve growth factor plays a divergent role in mediating growth of rat C6 glioma cells via binding to the p75 neurotrophin receptor.
Dysregulation of proliferation, differentiation and cell death play a major role in glial tumors, and there is evidence for regulatory mechanisms involving nerve growth factor (NGF) and its receptors in various CNS-derived tumor cell lines. The aim of our study was to observe the effect of exogenous recombinant NGF on C6 rat glioma growth, to characterize the role of endogenous NGF and the p75 neurotrophin receptor (p75) and to rule out whether p75 is necessary to mediate the effect of exogenous NGF. Recombinant exogenous NGF (1-100 ng/ml) was applied under different serum conditions (0%, 1%, 5%) and knockdown of endogenous NGF and p75 was achieved by lipid-mediated antisense oligonucleotide treatment. In presence of serum, NGF had a positive whereas in absence of serum NGF produced a negative effect on C6 cell number. A knockdown of NGF or p75 increased cell numbers and enhanced BrdU incorporation. In p75-knocked down cells NGF did not enhance C6 glioma growth in presence of serum. We conclude that (1) exogenous recombinant NGF enhances C6 glioma growth under serum conditions but decreases cell number in absence of serum, that (2) the effect of exogenous NGF is mediated by p75 alone or by heterodimers containing p75 and that (3) either basal levels of endogenous NGF or basal levels of p75 receptor moderate C6 glioma growth and represent an autoregulatory potential of C6 glioma cells.
Weis
Carla
C
Laboratory of Psychiatry, Clinic of Psychiatry, University Hospital Innsbruck, Austria.
Wiesenhofer
Bettina
B
Humpel
Christian
C
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005910:Glioma; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D001798:Blood Proteins; D016895:Culture Media, Serum-Free; D016376:Oligonucleotides, Antisense; D020800:Receptor, Nerve Growth Factor; D011994:Recombinant Proteins; D020932:Nerve Growth Factor