Cell-based selection provides novel molecular probes for cancer stem cells.

Cell-based selection provides novel molecular probes for cancer stem cells.
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DOI:
10.1002/ijc.27936
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发表时间:
2013-06-01
影响因子:
6.4
通讯作者:
Tan, Weihong
Tan, Weihong
中科院分区:
医学1区
文献类型:
--
作者:
Sefah, Kwame;Bae, Kyung-Mi;Phillips, Joseph A.;Siemann, Dietmar W.;Su, Zhen;McClellan, Steve;Vieweg, Johannes;Tan, Weihong

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癌症干细胞(CSC)代表分层组织的肿瘤中的恶性细胞亚群。它们构成肿瘤块内的恶性细胞亚群,并具有自我更新的能力,产生具有一组复杂的分化肿瘤细胞的异质肿瘤细胞群。 CSC可能是转移和治疗难治性疾病的原因。由于用于识别和分离纯 CSC 的标记物很少,我们使用基于细胞的指数富集配体系统进化 (cell-SELEX) 来创建 DNA 适体,可以识别活 CSC 表面的新分子靶标。在 22 个假定的 DNA 序列中,3 个与约 90% 的 DU145 前列腺癌细胞结合,5 个与约 15% 的 DU145 前列腺癌细胞结合。第二组适体呈阳性的 15% 细胞表达高水平的 E-钙粘蛋白和 CD44,具有高乙醛脱氢酶 1 活性,在非贴壁培养条件下生长为球体,并在免疫受损的小鼠中引发肿瘤。这些适体分子靶标的发现可以揭示新的 CSC 生物标志物。
Cancer stem cells (CSC) represent a malignant subpopulation of cells in hierarchically organized tumors. They constitute a sub-population of malignant cells within a tumor mass and possess the ability to self-renew giving rise to heterogeneous tumor cell populations with a complex set of differentiated tumor cells. CSC may be the cause of metastasis and therapeutic refractory disease. Because few markers exist to identify and isolate pure CSC, we used cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) to create DNA aptamers that can identify novel molecular targets on the surfaces of live CSC. Out of 22 putative DNA sequences, 3 bound to ~90% and 5 bound to ~15% of DU145 prostate cancer cells. The 15% of cells that were positive for the second panel of aptamers expressed high levels of E-cadherin and CD44, had high aldehyde dehydrogenase 1 activity, grew as spheroids under non-adherent culture conditions, and initiated tumors in immune-compromised mice. The discovery of the molecular targets of these aptamers could reveal novel CSC biomarkers.
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