Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells.

Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells.
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DOI:
10.1002/ijc.25967
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发表时间:
2012-01-01
影响因子:
6.4
通讯作者:
Zou, Weiping
Zou, Weiping
中科院分区:
医学1区
文献类型:
--
作者:
Kryczek, Ilona;Liu, Suling;Roh, Michael;Vatan, Linhua;Szeliga, Wojciech;Wei, Shuang;Banerjee, Mousumi;Mao, Yujun;Kotarski, Jan;Wicha, Max S.;Liu, Rebecca;Zou, Weiping

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癌症干细胞的鉴定对于推进癌症生物学和治疗至关重要。文献中利用CD24、CD44、CD117、CD133、ABCG、ESA和ALDH等标记物来鉴定和研究人类上皮性癌症干细胞。我们现在系统地分析和比较了这些标志物在新鲜卵巢上皮癌中的表达。尽管这些标志物的表达水平在来自不同供者的新鲜卵巢癌细胞中出乎意料地变化并且部分重叠,但我们可靠地在大多数新鲜卵巢癌中检测到CD133和ALDH的重要水平。此外,包括CD133和ALDH在内的大多数干细胞标记物在原代肿瘤细胞体外传代后逐渐丢失。然而,体外无血清培养和球培养以及免疫缺陷异种移植物体内传代可部分恢复ALDH和CD133的表达,而不能恢复CD24、CD44和CD117的表达。ALDH+和CD133+细胞比阴性细胞更有效地形成三维球体。这些球形细胞表达了高水平的干细胞核心基因转录物,并且在长期培养中可以扩增并形成额外的球体。来自新鲜肿瘤的ALDH+、CD133+和ALDH+CD133+细胞比来自阴性肿瘤的细胞更快地发展成更大的肿瘤。这种特性在异种移植肿瘤中得以保留。总之,这些数据表明,ALDH+和CD133+细胞富含卵巢癌起始(干细胞),ALDH和CD133可能被广泛用作研究卵巢癌干细胞生物学的可靠标记。
Identification of cancer stem cells is crucial for advancing cancer biology and therapy. Several markers including CD24, CD44, CD117, CD133, ABCG, ESA and ALDH are utilized to identify and investigate human epithelial cancer stem cells in the literature. We have now systemically analyzed and compared the expression of these markers in fresh ovarian epithelial carcinomas. Although the expression levels of these markers were unexpectedly variable and partially overlapping in fresh ovarian cancer cells from different donors, we reliably detected important levels of CD133 and ALDH in the majority of fresh ovarian cancer. Furthermore, most of these stem cell markers including CD133 and ALDH were gradually lost following in vitro passage of primary tumor cells. However, the expression of ALDH and CD133, but not CD24, CD44 and CD117, could be partially rescued by the in vitro serum free and sphere cultures, and the in vivo passage in the immune deficient xenografts. ALDH+ and CD133+ cells formed three dimensional spheres more efficiently than their negative counterparts. These sphere forming cells expressed high levels of stem cell core gene transcripts, and could be expanded and formed additional spheres in long-term culture. ALDH+, CD133+, and ALDH+CD133+ cells from fresh tumors developed larger tumors more rapidly than their negative counterparts. This property was preserved in the xenografted tumors. Altogether, the data suggest that ALDH+ and CD133+ cells are enriched with ovarian cancer initiating (stem) cells, and ALDH and CD133 may be widely utilized as reliable markers to investigate ovarian cancer stem cell biology.
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