CXCR4-Positive Subset of Glioma Is Enriched for Cancer Stem Cells

Authors: Zheng, Xuesheng; Xie, QingSong; Li, Shiting; Zhang, Wenchuan

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 1 December 2012, vol. 19, no. 12, pp. 555-561(7)

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Abstract:

CXC chemokine receptor 4 (CXCR4) is a cell surface molecule expressed in a distinct subset of glioma cells with enhanced tumorigenicity, and it is related to many important biological activities of the tumor. We supposed that this receptor might be a cell surface “marker” for glioma stem cells. This hypothesis was tested both in vitro and in vivo. The CXCR4+ and CXCR4 subsets were sorted from three human malignant glioma specimens. They were tested for the capability of colony formation in soft agar, generation of tumorosphere, self-renewal, and multipotent differentiation in vitro, and the capability of xenograft tumor in vivo. Drug and radiation resistance and coexpression with CD133 were studied for each subset. CXCR4+ glioma cells, but not CXCR4 cells, were capable of generating tumorospheres in serum-free medium. In addition, these spheres were able to self-renew after passage, and had multipotent differentiation after being induced in serum-containing medium. In soft agar assay, CXCR4+ cells generate much more colonies. The animal experiment revealed that CXCR4+ subpopulation had stronger tumorigenicity than the unsorted parental glioma cells, while the CXCR4 cells did not generate xenograft tumor. CXCR4-possitive cells were more resistant to temozolomide and radiation treatment. Both CXCR4+ and CXCR4 subsets contained very few CD133+ cells. The CXCR4+ subsets of glioma cells fulfill the standard of “cancer stem cell.”

Keywords: CXC chemokine receptor 4 (CXCR4); Cancer stem cell; Glioma

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504012X13340632812631

Publication date: December 1, 2012

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