Abstract:
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.
