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J Pathol ; 234(1): 23-33, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24756862

RESUMO

Cancer cells with enhanced self-renewal capacity influence tumour growth in glioblastoma. So far, a variety of surrogate markers have been proposed to enrich these cells, emphasizing the need to devise new characterization methods. Here, we screen a large panel of glioblastoma cultures (n = 21) cultivated under stem cell-permissive conditions and identify several cell lines with enhanced self-renewal capacity. These cell lines are capable of matrix-independent growth and form fast-growing, orthotopic tumours in mice. Employing isolation, re-plating, and label-retention techniques, we show that self-renewal potential of individual cells is partitioned asymmetrically between daughter cells in a robust and cell line-specific fashion. This yields populations of fast- and slow-cycling cells, which differ in the expression of cell cycle-associated transcripts. Intriguingly, fast-growing cells keep their slow-cycling counterparts in a reversible state of quiescence associated with high chemoresistance. Our results suggest that two different subpopulations of tumour cells contribute to aberrant growth and tumour recurrence after therapy in glioblastoma.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Hibridização Genômica Comparativa , Modelos Animais de Doenças , Dosagem de Genes/genética , Perfilação da Expressão Gênica , Glioblastoma/metabolismo , Humanos , Camundongos , Células-Tronco Neoplásicas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos
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