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Carcinogenesis Advance Access published online on July 20, 2005
Carcinogenesis, doi:10.1093/carcin/bgi182
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received October 13, 2004
Revised June 21, 2005
Accepted July 10, 2005

CANCER BIOLOGY

The chemokine GRO-{alpha} (CXCL1) confers increased tumorigenicity to glioma cells

Yan Zhou 1, Jing Zhang 1, Qiang Liu 2, Robert Bell 3, Daniel A. Muruve 4, Peter Forsyth 1, Mayi Arcellana-Panlilio 2, Stephen Robbins 5, and V. Wee Yong 1*

1 Department of Oncology, University of Calgary, Calgary, Alberta, Canada; Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
2 Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada
3 Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
4 Department of Medicine, University of Calgary, Calgary, Alberta, Canada
5 Department of Oncology, University of Calgary, Calgary, Alberta, Canada; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

* To whom correspondence should be addressed.
V. Wee Yong, E-mail: vyong{at}ucalgary.ca


  Abstract

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 over-express 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, {beta}1 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 to 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.


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