Regulators of G-protein signaling 3 and 4 (RGS3, RGS4) are associated with glioma cell motility.
Diffuse brain invasion is a major reason for poor prognosis of glioma patients. The molecular mechanisms underlying infiltration are different from those of other cancer types. To detect genes associated with glioma invasion, highly migratory clones were selected from U373MG glioma cells and from primary glioblastoma cells, and the gene expression pattern of these "fast" cells was compared with that of the original ("slow") cells using oligonucleotide microarrays comprising 12,625 genes. A total of 28 genes were differently expressed in both primary and established cell populations, including 19 genes that were upregulated and 9 that were downregulated in fast cells. Most of these genes have not been linked to glioma invasion so far. Specifically, differentially expressed genes included those encoding extracellular matrix components (COL16A1, DPT), proteases (CATD, PRSS11), cytokines (MDK, IL8), transport proteins (SLC1A3, ATP10B), cytoskeleton constituents (ACTA2, ACTSG, NEFL), DNA repair enzymes (WRN, ADPRTL2), and G-protein signaling components (GNA12, RGS3, RGS4). RGS3 and RGS4, which are homologs of the Drosophila glia gene loco, were further functionally analyzed. U373MG glioma cell clones overexpressing RGS3 or RGS4 showed an increase of both adhesion and migration. These findings expand the spectrum of possible molecular pathways underlying the invasion of neoplastic astrocytes. Specifically, they suggest that RGS proteins and G-protein-mediated signal transduction are evolutionary conserved functional players.
Tatenhorst
Lars
L
Institute of Neuropathology, University Hospital, Muenster, Germany.
Senner
Volker
V
Püttmann
Sylvia
S
Paulus
Werner
W
D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002999:Clone Cells / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; C485898:RGS3 protein, human; C415085:Rgs3 protein, mouse; C098799:RGS4 protein; D019204:GTP-Binding Proteins