Nerve growth factor and cyclic AMP: Opposite effects on neuroblastoma-substrate adhesion

I. Schulze, J. R. Perez Polo

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Increased cellular adhesion has been postulated to be an early event required of neuroblasts undergoing neurite extension during differentiation. Nerve growth factor (NGF) induces neurite extension in a variety of cell types of neural crest origin. In the PC12 rate pheochromocytoma cell line, which has been proposed as a model for precursor cells to sympathetic neurons, NGF and dibutyryl cyclic AMP (dBcAMP) promote both neurite extension and an increased rat of cell-substrate adhesion. Since dBcAMP can substitute for NGF in this enhancement of adhesion rate in the PC12 cell line, cAMP has been suggested as a second messenger for NGF. We have shown that in two nearly diploid adrenergic like human neuroblastoma clones, the KA and SY5Y cell lines, which also extend neurites in response to both NGF and dBcAMP, only NGF enhances cellular adhesion, as defined by an increase in the number of cells prelabeled with 35S-methionine which attach to culture dishes at a given time. Incubation with monospecific antibodies directed against murine β-NGF abolishes the NGF effect on adhesion. The NGF effect on human neuroblastoma is specific insofar as NGF does not facilitate adhesion of two glioma lines. Unlike the results obtained for PC12, in both SY5Y and KA lines, 1 mM dBcAMP decreases the rate of adhesion to levels significantly below those of controls. Adhesiveness of neuroblastoma cells treated with both NGF and dBcAMP is intermediate between that of cells treated with either agent alone. While theophylline mimics the dBcAMP effect, sodium butyrate has no such effect. At 22°C, the effect of NGF on neuroblastoma substrate adhesion is observable within 5 minutes and persists for 2 hours; treatment of the KA line with NGF at 37°C for 24 hours results in a more persistent enhancement of cell adhesion. Furthermore, both SY5Y and KA exhibit different morphologies when challenged with NGF, dBcAMP, or sodium butyrate. This study suggests that NGF and cyclic AMP do not share a common mechanism of action, but can in fact interact antagonistically in an adrenergic like neuroblastoma model system. Furthermore, the results suggest that increased cellular adhesiveness may not be an obligatory prerequisite for neurite extension by neuroblasts in development.

    Original languageEnglish (US)
    Pages (from-to)393-411
    Number of pages19
    JournalJournal of Neuroscience Research
    Volume8
    Issue number2-3
    StatePublished - 1982

    Fingerprint

    Nerve Growth Factor
    Neuroblastoma
    Cyclic AMP
    Bucladesine
    Neurites
    Adhesiveness
    Butyric Acid
    PC12 Cells
    Cell Adhesion
    Adrenergic Agents
    Cell Line
    Neural Crest
    Second Messenger Systems
    Theophylline
    Diploidy
    Glioma
    Methionine

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Nerve growth factor and cyclic AMP : Opposite effects on neuroblastoma-substrate adhesion. / Schulze, I.; Perez Polo, J. R.

    In: Journal of Neuroscience Research, Vol. 8, No. 2-3, 1982, p. 393-411.

    Research output: Contribution to journalArticle

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