The chemokine GRO-alpha (CXCL1) confers increased tumorigenicity to glioma cells.
The chemokine GRO-alpha (CXCL1) has been found to mediate the proliferation of glia progenitor cells during neural development. As malignant gliomas are thought to arise from glia progenitors or their differentiated counterparts, astrocytes or oligodendrocytes, we have investigated whether GRO-alpha regulates the tumor characteristics of glioma cells. We found first that resected glioma specimens were strongly immunoreactive for GRO-alpha expression in cells with the morphology of tumor cells. In culture, the U251 glioma line transfected to overexpress GRO-alpha had elevated levels of motility and invasiveness. GRO-alpha transfectants increased their expression of several proteins associated with migratory behavior, including matrix metalloproteinase-2, beta1-integrin and SPARC. The implantation of GRO-alpha glioma clones into the brain of nude mice caused the early demise of mice and this was associated with the formation of larger intracerebral tumors when compared with mice implanted with vector control lines. These results implicate GRO-alpha in gliomas and suggest that the dysregulation of a glia proliferative factor contributes to tumorigenesis. Targeting GRO-alpha may be a useful therapeutic tool to control brain tumor biology.
Zhou
Yan
Y
Department of Oncology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Zhang
Jing
J
Liu
Qiang
Q
Bell
Robert
R
Muruve
Daniel A
DA
Forsyth
Peter
P
Arcellana-Panlilio
Mayi
M
Robbins
Stephen
S
Yong
V Wee
VW
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019012:Integrin beta1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; D015676:Osteonectin; D020778:Matrix Metalloproteinase 2