Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line

Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line
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DOI:
10.1073/pnas.0307618100
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发表时间:
2004-01-20
影响因子:
11.1
通讯作者:
Taga, T
Taga, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kondo, T;Setoguchi, T;Taga, T

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干细胞和癌细胞都被认为能够无限增殖。然而,矛盾的是,一些癌症似乎含有干细胞样细胞(癌症干细胞)。为了帮助解决这一悖论,我们研究了已在培养物中维持多年的已建立的恶性细胞系是否含有干细胞亚群。在这篇文章中,我们表明许多癌细胞系含有一个小的侧群(SP),在许多正常组织中,它被认为含有组织的干细胞。我们证明,在没有血清的情况下,碱性成纤维细胞生长因子和血小板衍生生长因子的组合可以维持 C6 神经胶质瘤细胞系中的 SP 细胞。此外,我们表明,C6 SP 细胞(而非非 SP 细胞)可以在培养物中产生 SP 和非 SP 细胞,并且在很大程度上导致该细胞系的体内恶性肿瘤。最后,我们提供了证据表明 C6 SP 细胞可以在体外和体内产生神经元和神经胶质细胞。我们认为,许多癌细胞系都含有少量干细胞亚群,这些干细胞亚群富含 SP,可以在培养物中无限期维持,并且对其恶性肿瘤至关重要。
Both stem cells and cancer cells are thought to be capable of unlimited proliferation. Paradoxically, however, some cancers seem to contain stem-like cells (cancer stem cells). To help resolve this paradox, we investigated whether established malignant cell lines, which have been maintained for years in culture, contain a subpopulation of stem cells. In this article, we show that many cancer cell lines contain a small side population (SP), which, in many normal tissues, is thought to contain the stem cells of the tissue. We demonstrate that in the absence of serum the combination of basic fibroblast growth factor and platelet-derived growth factor maintains SP cells in the C6 glioma cell line. Moreover, we show that C6 SP cells, but not non-SP cells, can generate both SP and non-SP cells in culture and are largely responsible for thein vivomalignancy of this cell line. Finally, we provide evidence that C6 SP cells can produce both neurons and glial cellsin vitroandin vivo. We propose that many cancer cell lines contain a minor subpopulation of stem cells that is enriched in an SP, can be maintained indefinitely in culture, and is crucial for their malignancy.