TrkA expression decreases the in vivo aggressiveness of C6 glioma cells.
We stably expressed the nerve growth factor receptor trkA or a truncated trkA lacking the kinase domain (trkA delta) in a highly tumorigenic rat glioma cell line, C6. Survival of rats with large intrastriatal inocula of C6trkA cells was significantly longer than for rats bearing C6 or C6trkA delta cells. Histological studies revealed that C6trkA cells were much less invasive than C6 or C6trkA delta cells and had a greater rate of apoptosis. There was no apparent induction of differentiation of C6 cells by trkA. Therefore, unlike what is observed in neuroblastomas, trkA decreases tumorigenicity by modulating invasiveness and tumor cell death independent of inducing differentiation. This novel mechanism suggests a new therapeutic strategy for malignant gliomas.
Lachyankar
M B
MB
Worcester Foundation for Biomedical Research, University of Massachusetts Medical Center 01655, USA.
Ross
A H
AH
Litofsky
N S
NS
Condon
P J
PJ
Quesenberry
P J
PJ
Recht
L D
LD
D000818:Animals; D005910:Glioma / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA