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A distinct subset of glioma cell lines with stem cell‐like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target
Author(s) -
Schulte Alexander,
Günther Hauke S.,
Phillips Heidi S.,
Kemming Dirk,
Martens Tobias,
Kharbanda Samir,
Soriano Robert H.,
Modrusan Zora,
Zapf Svenja,
Westphal Manfred,
Lamszus Katrin
Publication year - 2011
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21127
Subject(s) - biology , cell culture , cxcr4 , phenotype , stem cell , cancer research , glioma , gene expression profiling , cancer stem cell , in vivo , gene signature , gene expression , microbiology and biotechnology , gene , genetics , receptor , chemokine
Abstract Glioblastomas contain stem‐like cells that can be maintained in vitro using specific serum‐free conditions. We investigated whether glioblastoma stem‐like (GS) cell lines preserve the expression phenotype of human glioblastomas more closely than conventional glioma cell lines. Expression profiling revealed that a distinct subset of GS lines, which displayed a full stem‐like 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 in vivo , express CD133, grow spherically in vitro , 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‐like 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 “stemness”. 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 hi cells, a subfraction of which coexpressed CD133 and was expandable by hypoxia, whereas conventional cell lines contained only CXCR4 lo cells. Convection‐enhanced local treatment with AMD3100, a specific CXCR4 antagonist, inhibited the highly invasive growth of GS xenografts in vivo and cell migration in vitro . 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‐initiating glioma stem cells in vivo . © 2011 Wiley‐Liss, Inc.