An anti-apoptotic role for NGF receptors in human rhabdomyosarcoma.
The expression and biological function of Nerve Growth Factor (NGF) receptors was studied in a panel of rhabdomyosarcoma cell lines derived from embryonal and alveolar histotype. All the cell lines expressed both the high affinity receptor TrkA and the low affinity receptor p75(NTR). Treatment with exogenous NGF did not considerably alter rhabdomyosarcoma cell growth or differentiation, but significantly inhibited spontaneous apoptosis as well as apoptosis, and induced by serum starvation or apoptosis induced by treatment with cycloheximide (CHX). Rhabdomyosarcoma cell lines expressed NGF and other neurotrophins and trace amounts of NGF protein were found in the supernatants of rhabdomyosarcoma cell cultures. Blocking the putative autocrine loop with an anti-NGF antibody resulted in an increase in apoptosis compared with control cultures. These data suggest that the simultaneous presence of both high and low affinity NGF receptors engaged by endogenous or exogenous NGF might contribute to the escape from apoptosis exhibited by the rhabdomyosarcoma cells.
Astolfi
A
A
Department of Experimental Pathology, Section of Cancer Research, University of Bologna, viale Filopanti 22, I-40126, Bologna, Italy.
Nanni
P
P
Landuzzi
L
L
Ricci
C
C
Nicoletti
G
G
Rossi
I
I
Lollini
P L
PL
De Giovanni
C
C
D017209:Apoptosis / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism / Q000502:physiology*; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA