<p class="first" id="P2">Neural progenitor cell (NPC) fate is influenced by a variety
of biological cues elicited
from the surrounding microenvironment and recent studies suggest their possible role
in pediatric glioblastoma multiforme (GBM) development. Since a few GBM cells also
display NPC characteristics, it is not clear whether NPCs transform to tumor cell
phenotype leading to the onset of GBM formation, or NPCs migrate to developing tumor
sites in response to paracrine signaling from GBM cells. Elucidating the paracrine
interactions between GBM cells and NPCs
<i>in vivo</i> is challenging due to the inherent complexity of the CNS. Here, we
investigated the
interactions between human NPCs (ReNcell) and human pediatric GBM-derived cells (SJ-GBM2)
using a Transwell
<sup>®</sup> coculture setup to assess the effects of GBM cells on ReNcells (cytokine
and chemokine
release, viability, phenotype, differentiation, migration). Standalone ReNcell or
GBM cultures served as controls. Qualitative and quantitative results from ELISA
<sup>®</sup>, Live/Dead
<sup>®</sup> and BrdU assays, immunofluorescence labeling, western blot analysis,
and scratch
test suggests that although ReNcell viability remained unaffected in the presence
of pediatric GBM cells, their morphology, phenotype, differentiation patterns, neurite
outgrowth, migration patterns (average speed, distance, number of cells) and GSK-3β
expression were significantly influenced. The cumulative distance migrated by the
cells in each condition was fit to Furth’s formula, derived formally from Ornstein-Uhlenbeck
process. ReNcell differentiation into neural lineage was compromised and astrogenesis
promoted within cocultures. Such coculture platform could be extended to identify
the specific molecules contributing to the observed phenomena, to investigate whether
NPCs could be transplanted to replace lesions of excised tumor sites, and to elucidate
the underlying molecular pathways involved in GBM-NPC interactions within the tumor
microenvironment.
</p>