Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
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DOI：
10.1016/j.ygyno.2016.03.022
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发表时间：
2016-08
影响因子：
4.7
通讯作者：
Jones RJ
中科院分区：
文献类型：
--
作者：
Sharrow AC;Perkins B;Collector MI;Yu W;Simons BW;Jones RJ
癌症干细胞 (CSC) 范式假设，临床上成功根除 CSC 可能会导致卵巢癌患者获得持久缓解。尽管有越来越多的证据支持卵巢 CSC，但其表型和临床相关性仍不清楚。我们和其他人发现多种正常和恶性干细胞中乙醛脱氢酶 1 (ALDHhigh) 表达较高，并试图更好地表征卵巢癌中的 ALDHhigh 细胞。我们比较了代表不同亚型的两种卵巢癌模型中的 ALDHhigh 和 ALDHlow 细胞：源自自发性大鼠子宫内膜样癌的 FNAR-C1 细胞和人 SKOV3 细胞系（被描述为浆液性和透明细胞亚型）。我们评估了这些群体的干细胞特征，然后通过微阵列和 qPCR 分析了表达。 ALDHhigh 细胞表现出 CSC 特性，包括：较小的尺寸、静止、体外再生细胞系的表型多样性、缺乏接触抑制、非贴壁生长、多药耐药性和体内致瘤性。对其他人报道的用于富集卵巢 CSC 的标记物表达进行微阵列和 qPCR 分析表明，两种模型的 ALDHhigh 细胞均显示 CD24 下调，但 CD44、KIT 和 CD133 的表达不一致。然而，以下药物靶点在两种模型的 ALDHhigh 细胞中一致表达：mTOR 信号传导、her-2/neu、CD47 和 FGF18 / FGFR3。根据功能特征，ALDH 高卵巢癌细胞代表卵巢 CSC 群体。差异基因表达确定了可药物靶点，这些靶点具有针对多种亚型卵巢 CSC 的治疗功效的潜力。
The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDHhigh) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDHhigh cells in ovarian cancer. We compared ALDHhigh to ALDHlow cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDHhigh cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDHhigh cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following drugable targets were consistently expressed in the ALDHhigh cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18 / FGFR3. Based on functional characterization, ALDHhigh ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified drugable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes.
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脾酪氨酸激酶的抑制通过稳定微管通过稳定卵巢癌细胞中紫杉醇诱导的细胞毒性。
影响因子：
50.3
作者：
Yu Y;Gaillard S;Phillip JM;Huang TC;Pinto SM;Tessarollo NG;Zhang Z;Pandey A;Wirtz D;Ayhan A;Davidson B;Wang TL;Shih IeM
通讯作者：
Shih IeM
DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
11.2
作者：
Matsui, William;Wang, Qiuju;Jones, Richard J.
通讯作者：
Jones, Richard J.
具有 CD117 表型的卵巢癌细胞具有高度致瘤性，并且与化疗结果相关
影响因子：
3.6
作者：
Luo, Lijing;Zeng, Jianfang;Shen, Keng
通讯作者：
Shen, Keng
影响因子：
20.3
作者：
Jones, Richard J.;Gocke, Christopher D.;Matsui, William
通讯作者：
Matsui, William