An anti-apoptotic role for NGF receptors in human rhabdomyosarcoma

The expression and biological function of Nerve Growth Factor (NGF) recepto rs was studied in a panel of rhabdomyosarcoma cell lines derived from embry onal and alveolar histotype. All the cell lines expressed both the high aff inity receptor TrkA and the low affinity receptor p75(NTR). Treatment with exogenous NGF did not considerably alter rhabdomyosarcoma cell growth or di fferentiation, but significantly inhibited spontaneous apoptosis as well as apoptosis, and induced by serum starvation or apoptosis induced by treatme nt with cycloheximide (CHX). Rhabdomyosarcoma cell lines expressed NGF and other neurotrophins and trace amounts of NGF protein were found in the supe rnatants of rhabdomyosarcoma cell cultures. Blocking the putative autocrine loop with an anti-NGF antibody resulted in an increase in apoptosis compar ed with control cultures. These data suggest that the simultaneous presence of both high and low affinity NGF receptors engaged by endogenous or exoge nous NGF might contribute to the escape from apoptosis exhibited by the rha bdomyosarcoma cells. (C) 2001 Elsevier Science Ltd. All rights reserved.