CXCR4-positive subset of glioma is enriched for cancer stem cells.
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".
Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China. xueshengzheng@gmail.com
Xuesheng
X
Zheng
QingSong
Q
Xie
Shiting
S
Li
Wenchuan
W
Zhang
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D010455:Peptides / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D000077204:Temozolomide; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000071916:AC133 Antigen; D015703:Antigens, CD; D018906:Antineoplastic Agents, Alkylating; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019718:Receptors, CXCR4; D003606:Dacarbazine; D000077204:Temozolomide