Role of Glia Maturation Factor beta (GMFj3) in Differentiation of the Childhood Cancer Neuroblastoma

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Richards, Ceri
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Background: Neuroblastoma (NB), the second most common solid tumor of the peripheral nervous system, accounts for 10% of pediatric cancers. Most children present with advanced stage disease with very poor survival rates. 13-cis retinoic acid (RA), a differentiating factor, is a component of NB treatment following surgery, radiation and chemotherapy. Glia Maturation Factor beta (GMFj3) was initially characterized as a factor that caused process extension and reduced cell proliferation when added to glioblastoma cells. GMFB as an actin depolymerizing factor (ADF) may modify cell morphology by interacting with the peripheral actin cytoskeleton localized within the distal axon. GMFi3 is highly expressed in neuronal tumor-derived cell lines, especially NB. Results: GMFJ3 phosphorylation was shown to decrease with RA treatment of NB cell lines. GMFJ3 was hypophosphorylated in adult mouse brain tissues. GMFJ3 transfection showed modest increases in differentiation in NB cell lines as demonstrated in a neurite extension assay. A possible GMF-j3 dimer is formed with dephosphorylation of NB cells and in more differentiated mouse tissues. A MYCN-amplified NB cell line has increased GMFJ3 expression. Conclusions: Our results are consistent with the role of GMFJ3 as an ADF, since ADFs function when dephosphorylated. These experiments support a relationship between GMFJ3 phosphorylation and differentiation of NB cell lines. Examination of the role of GMFi3 as an ADF in NB differentiation may ultimately contribute towards novel biological therapies directed against this highly malignant childhood tumor.