Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance.
Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance.
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DOI：
10.4161/cc.8.1.7533
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Mor G
中科院分区：
文献类型：
--
作者：
Alvero AB;Chen R;Fu HH;Montagna M;Schwartz PE;Rutherford T;Silasi DA;Steffensen KD;Waldstrom M;Visintin I;Mor G
卵巢癌治疗的一个主要负担是高复发率和化疗耐药性。癌症干细胞（CSC）提供了一个可以自我更新的细胞库，通过产生分化的细胞（非干细胞）来维持肿瘤，这些细胞构成了肿瘤的大部分，并且可能是复发的主要来源。我们描述了人卵巢癌干细胞（OCSCs）的特征。这些细胞具有独特的遗传特征，使它们具有重现原始肿瘤、在化疗中增殖和促进复发的能力。在从腹水和实体瘤分离的细胞中鉴定的CSC的特征在于：CD 44+、MyD 88+、组成型NFκB活性和细胞因子和趋化因子产生、高修复能力、对常规化疗的化学抗性、对TNFα介导的细胞凋亡的抗性、在悬浮液中形成球状体的能力以及在体内重现原始肿瘤的能力。化疗消除了大部分肿瘤，但留下了具有高修复和更新能力的癌细胞核心。在这些细胞中鉴定的分子特性可以解释CSC控制自我更新和驱动转移的一些独特特征。人OCSC的鉴定和克隆有助于为卵巢癌患者开发更好的治疗方法。
A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, maintain the tumor by generating differentiated cells (non-stem cells) which make up the bulk of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence. CSC identified in cells isolated form ascites and solid tumors are characterized by: CD44+, MyD88+, constitutive NFκB activity and cytokine and chemokine production, high capacity for repair, chemoresistance to conventional chemotherapies, resistance to TNFα-mediated apoptosis, capacity to form spheroids in suspension, and ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique characteristics of CSCs that control self-renewal and drive metastasis. The identification and cloning of human OCSCs can aid in the development of better therapeutic approaches for ovarian cancer patients.
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影响因子：
3.6
作者：
Leung, Chung-Hang;Grill, Susan P.;Cheng, Yung-Chi
通讯作者：
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DOI：
10.1152/ajpgi.00328.2004
发表时间：
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