Effect Of Growth Factors On Differentiation And Growth Of Human Cancer Cells

Part I: Effect of nerve growth factor (NGF) and its receptors on differentiation of human neuroblastoma and neuroepithelioma cell lines.Eighteen neuroblastoma and neuroepithelioma cell lines were screened for nerve growth factor (NGF) induced differentiation. All 3 neuroepithelioma cell lines and all 9 neuroblastoma cell lines with amplified N-myc oncogene did not show any apparent NGF-induced differentiation. However,neurite extension was observed for 3 of 6 neuroblastoma cell lines with single-copy N-myc oncogene.The three responsive lines had a neuronal phenotype (N type) which was enhanced by the addition of NGF. The three nonresponsive cell lines in this group were all epithelial phenotype (S type). The addition of NGF to the responsive cell lines resulted in an up-regulation of neurofilament light chain (NF-L) mRNA express ion. Results of chemical cross linking of NGF receptor, binding of NGF to cell lines analysed by the method of Scatchard and Flow Cytometry revealed that there was a certain amount of two classes of NGF receptors in responsive cell lines.As shown by Northern Blot,NGF receptor mRNA was expressed in responsive cell lines but not in nonresponsive cell lines. NGF had no apparent effect on NGF receptor mRNA expression. All of the neuroepithelioma cell lines which were epithlial phenotype (S type),did not respond to NGF. Studies of expression of mRNA of neuronal markers by Northern Blotting technique showed that there was no expression of neurofilament light chain (NF-L), chromogranin A (CGA), neuropeptide Y (NPY), peripherin, synapsin and neurotensin (NT) mRNA's in all 3 neuroepithelioma cell lines.All neuroblastoma cell lines expressed NF-L mRNA, some of them also express CGA and NPY mRNA. Epidermal growth factor receptor (EGFR) mRNA was found in S type neuroblastoma cell lines, but not in N type and intermediate type (I type) dominated cell line SHSY5Y.