CD133+ and nestin+ tumor-initiating cells dominate in N29 and N32 experimental gliomas.

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CD133+ and nestin+ tumor-initiating cells dominate in N29 and N32 experimental gliomas. / Bexell, Daniel; Gunnarsson, Salina; Siesjö, Peter; Bengzon, Johan; Darabi, Anna.

I: International Journal of Cancer, Vol. 125, Nr. 1, 2009, s. 15-22.

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T1 - CD133+ and nestin+ tumor-initiating cells dominate in N29 and N32 experimental gliomas.

AU - Bexell, Daniel

AU - Gunnarsson, Salina

AU - Siesjö, Peter

AU - Bengzon, Johan

AU - Darabi, Anna

PY - 2009

Y1 - 2009

N2 - The current study was designed to critically evaluate the notion that cancer stem cell (CSC)-like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, betaIII-tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. Unsorted adherently grown cells displayed very high clonogenicity in vitro and robust tumorigenicity in vivo. Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC-like cells in glioma models: sphere-formation is not a prerequisite for accumulation of tumorigenic cells, and CSC-like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor-initiating CSC-like cells. (c) 2009 Wiley-Liss, Inc.

AB - The current study was designed to critically evaluate the notion that cancer stem cell (CSC)-like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, betaIII-tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. Unsorted adherently grown cells displayed very high clonogenicity in vitro and robust tumorigenicity in vivo. Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC-like cells in glioma models: sphere-formation is not a prerequisite for accumulation of tumorigenic cells, and CSC-like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor-initiating CSC-like cells. (c) 2009 Wiley-Liss, Inc.

KW - glioma

KW - cancer stem cell

KW - rat

KW - tumor

KW - CD133

KW - nestin

U2 - 10.1002/ijc.24306

DO - 10.1002/ijc.24306

M3 - Article

VL - 125

SP - 15

EP - 22

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 1

ER -