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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Integrin up-regulation as marker of neuroblastoma cell differentiation: correlation with neurite extension.

We have characterized the adhesion properties, integrin expression, and morphological changes due to extracellular matrix (ECM)-integrin interactions in a neuronal model. We showed that a modulation of some integrin heterodimers occurs during interferon-gamma (IFN-gamma) induced neuroblastoma ( NB) cell differentiation. To better elucidate the possible implication and function of integrin receptors during neuronal maturation, we analyzed the changes in integrin expression in two human NB cell lines, LAN-5 and GI-LI-N, which represent different stages of neuronal differentiation. These models show opposite morphological maturation after interferon-gamma and tumor necrosis factor-alpha (IFN-gamma+TNF) treatment. While LAN-5 cells acquired the ability to extend long and branched neurites, GI-LI-N cells did not. Both cell lines showed enhanced expression of phenotypical and biochemical markers of neural maturation. Moreover, retinoic acid (RA) had different effects on the two NB cell lines: on LAN-5 cells it acts as a differentiation-promoting agent, while on GI-LI-N cells it has an antiproliferative effect, driving them to apoptosis. RT-PCR experiments and immunoprecipitation assays showed a late but marked increase in the expression of alpha1, alpha2, alpha3, and beta1 chains after IFN-gamma+TNF treatment of LAN-5 cells, and only alpha1 and beta1 chains upon RA induction. Treatment with IFN-gamma+TNF induced GI-LI-N cells to show only a late and remarkable increase of alpha1/beta1 heterodimer; on the contrary, RA treatment caused a decrease in all integrin chains. These changes are accompanied in differentiated cells by substantial increases in cell attachment to all purified ECM components tested and an increase of neurite-bearing cells and of average neurite length. In conclusion, these findings indicate a close correlation between up-regulation of integrins and neuronal morphogenesis.[1]


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