Astrocytes enhance the invasion potential of glioblastoma stem-like cells.
Glioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to the invasive phenotype, however, has not been completely defined. Towards this end, we have defined the invasion potential of CD133+ GSCs and their differentiated CD133- counterparts grown under standard in vitro conditions and in co-culture with astrocytes. Using a trans-well assay, astrocytes or astrocyte conditioned media in the bottom chamber significantly increased the invasion of GSCs yet had no effect on CD133- cells. In addition, a monolayer invasion assay showed that the GSCs invaded farther into an astrocyte monolayer than their differentiated progeny. Gene expression profiles were generated from two GSC lines grown in trans-well culture with astrocytes in the bottom chamber or directly in contact with astrocyte monolayers. In each co-culture model, genes whose expression was commonly increased in both GSC lines involved cell movement and included a number of genes that have been previously associated with tumor cell invasion. Similar gene expression modifications were not detected in CD133- cells co-cultured under the same conditions with astrocytes. Finally, evaluation of the secretome of astrocytes grown in monolayer identified a number of chemokines and cytokines associated with tumor cell invasion. These data suggest that astrocytes enhance the invasion of CD133+ GSCs and provide additional support for a critical role of brain microenvironment in the regulation of GBM biology.
Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
Barbara H
BH
Rath
Joshlean M
JM
Fair
Muhammad
M
Jamal
Kevin
K
Camphausen
Philip J
PJ
Tofilon
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D017348:Microscopy, Electron, Scanning Transmission; D009361:Neoplasm Invasiveness / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D059467:Transcriptome; D059016:Tumor Microenvironment
D000071916:AC133 Antigen; D015703:Antigens, CD; D017077:Culture Media, Conditioned; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides