Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation.
Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation.
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DOI：
10.1002/stem.271
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发表时间：
2010-03-31
期刊：
影响因子：
5.2
通讯作者：
Farrar, William L.
中科院分区：
文献类型：
--
作者：
Hurt, Elaine M.;Chan, King;Duhagon Serrat, Maria Ana;Thomas, Suneetha B.;Veenstra, Timothy D.;Farrar, William L.
关键词：
越来越多的证据表明，肿瘤是由一种称为癌症干细胞（CSCs）的罕见细胞亚群引发的。CSCs通常是静止的，自我更新的，形成肿瘤的数量很少，并且在肿瘤中产生异质细胞类型。从多种肿瘤类型中分离出来的CSCs在体内和体外血清培养时都能分化，但导致其分化的因素尚未确定。本研究表明，玻璃体连接蛋白是人血清中通过整合素α v β3依赖机制驱动干细胞分化的成分。玻璃体连接蛋白培养的CSCs导致干细胞基因下调，分化标记物调节，β-catenin核定位缺失。阻断整合素αVβ3抑制分化和随后的肿瘤形成。因此，CSCs必须通过一个或多个细胞外信号来分化和启动肿瘤形成，这为未来针对外部和细胞内途径的新疗法定义了一个新的轴。
There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem cells (CSCs). CSCs are generally quiescent, self-renew, form tumors at low numbers, and give rise to the heterogeneous cell types found within a tumor. CSCs isolated from multiple tumor types differentiate both in vivo and in vitro when cultured in serum, yet the factors responsible for their differentiation have not yet been identified. Here we show that vitronectin is the component of human serum driving stem cell differentiation through an integrin αVβ3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of β-catenin nuclear localization. Blocking integrin αVβ3 inhibits differentiation and subsequently tumor formation. Thus, CSCs must be engaged by one or more extracellular signals to differentiate and initiate tumor formation, defining a new axis for future novel therapies aimed at both the extrinsic and intracellular pathways.
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影响因子：
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