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Expression profiling revealed that a distinct subset of GS lines, which displayed a full stem\u2010like phenotype (GSf), mirrored the expression signature of glioblastomas more closely than either other GS lines or cell lines grown in serum. GSf lines are highly tumorigenic and invasive <jats:italic>in vivo<\/jats:italic>, express CD133, grow spherically <jats:italic>in vitro<\/jats:italic>, are multipotent and display a Proneural gene expression signature, thus recapitulating key functional and transcriptional aspects of human glioblastomas. In contrast, GS lines with a restricted stem\u2010like phenotype exhibited expression signatures more similar to conventional cell lines than to original patient tumors, suggesting that the transcriptional resemblance between GS lines and tumors is associated with different degrees of \u201cstemness\u201d. Among markers overexpressed in patient tumors and GSf lines, we identified CXCR4 as a potential therapeutic target. GSf lines contained a minor population of CXCR4<jats:sup>hi<\/jats:sup> cells, a subfraction of which coexpressed CD133 and was expandable by hypoxia, whereas conventional cell lines contained only CXCR4<jats:sup>lo<\/jats:sup> cells. Convection\u2010enhanced local treatment with AMD3100, a specific CXCR4 antagonist, inhibited the highly invasive growth of GS xenografts <jats:italic>in vivo<\/jats:italic> and cell migration <jats:italic>in vitro<\/jats:italic>. We thus demonstrate the utility of GSf lines in testing therapeutic agents and validate CXCR4 as a target to block the growth of invasive tumor\u2010initiating glioma stem cells <jats:italic>in vivo<\/jats:italic>. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.21127","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T21:23:08Z","timestamp":1296768188000},"page":"590-602","source":"Crossref","is-referenced-by-count":115,"title":["A distinct subset of glioma cell lines with stem cell\u2010like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target"],"prefix":"10.1002","volume":"59","author":[{"given":"Alexander","family":"Schulte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke S.","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi 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