Effects of ectopic expression of the L1CAM long ectodomain in astrotypic human neural progenitor cells on motility, proliferation and differentiation
Date
2011
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Publisher
University of Delaware
Abstract
Astrotypic human neural progenitor (AHNP) cells have been implicated as a potential source of cancer forming cells, along with neural stem cells in current literature. AHNPs have a reduced differentiation potential relative to stem cells however, differentiation of several cell types can be induced with in vitro culturing conditions. Whether these cells are tumorogenic remains unclear, however this study indicates an increased differentiation potential as oligodendrocyte precursors were found when cultured with avian brain aggregates. This study aims to identify the effect of L1 cell adhesion molecule (L1CAM) on astrotypic human neural progenitor cells. A transformation of these progenitor cells could induce new glioma-like phenotype. Furthermore, L1CAM is found at the leading edge of invasive colon tumors and is a prognostic indicator in the serum of ovarian cancer patients, and in glioblastoma multiforme (GBM). L1CAM is normally only seen in the nerves of the central nervous system but has been found in several GBM patient surgical samples, in human glioma cell lines, and in AHNPs. Studies from our lab have implicated L1CAM as a stimulator of cell motility and invasiveness. Overexpressing L1CAM's extracellular domain (~180 kDa) in the AHNP cell lines show no change in motility in vitro. Furthermore L1LE overexpressing AHNPs showed altered proliferation especially when growth factors were removed. Normal AHNPs were cultured in vitro and with chick embryonic brain cell aggregates to show increased differentiation potential.