Nerve growth factor receptor expression in medulloblastomas and the potential role of nerve growth factor as a differentiating agent in medulloblastoma cell lines.
Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and nonneoplastic cell lines. In this study, our aim was to determine NGF receptor (NGFr) status in medulloblastoma specimens and cell lines and to investigate whether NGF could act as a potential differentiating agent for this common pediatric brain tumor. Paraffin-embedded tumor tissue from 10 patients with the diagnosis of medulloblastoma was retrospectively analyzed to determine the frequency of NGFr expression. Of the 10 tumor specimens evaluated, 4 were positive for NGFr; however, NGFr staining was confined to only 5 to 8% of the cells in a randomly scattered pattern. No colocalization was present with neuronal, glial, or vascular structures. In addition, two medulloblastoma cell lines established in our laboratory were also evaluated for NGFr. In this study, we also examined the effects of retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate, and NGF on medulloblastoma cell lines to evaluate their effect on morphological differentiation and NGFr expression. Although these agents failed to cause NGFr expression in our cell lines, morphological alteration was noticed in only one of the cell lines with retinoic acid. Therefore, because of the lack of de novo or induced NGFr expression, it is unlikely that NGF will be useful as a potential therapeutic differentiating agent for medulloblastomas.
Keles
G E
GE
Department of Neurological Surgery, University of Washington Medical Center, Seattle.
Berger
M S
MS
Schofield
D
D
Bothwell
M
M
D000293:Adolescent; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology*
D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate