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趋化因子受体作为靶向消除神经胶质瘤干细胞的药理学靶点。

Chemoattractant receptors as pharmacological targets for elimination of glioma stem-like cells.

机构信息

Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.

出版信息

Int Immunopharmacol. 2011 Dec;11(12):1961-6. doi: 10.1016/j.intimp.2011.08.021. Epub 2011 Sep 17.

Abstract

Malignant tumors are thought to be initiated by a small population of cells that display stem cell properties, including the capacity of self-renewal, multipotent differentiation, initiation of tumor tissues and resistance to therapy. Cancer stem cells (CSCs) have also been identified in gliomas in which they are named as glioma stem-like cells (GSLCs), or glioma stem cells. In xenograft transplantation models, GSLCs propagate tumor and promote tumor progression. The tumorigenesis of GSLCs depends not only on their autonomous proliferation but also on interaction with microenvironment components. Among these components, G protein coupled chemoattractant receptors (GPCRs) and their agonists have attracted much attention for their capacity to mediate leukocyte infiltration, angiogenesis, tumor invasion and metastasis. Chemoattractant GPCRs are widely expressed by tumor cells and stromal cells and recognize agonists present in the tumor microenvironment. Such GPCRs have been found to be expressed also by CSCs including GSLCs. In this brief review, we will summarize the recent development in the studies of the function, regulation and signal transduction of chemoattractant GPCRs in GSLCs in hope to promote a better understanding of the mechanistic basis of the progression of gliomas and the identification of molecular targets for the novel anti-glioma therapy.

摘要

恶性肿瘤被认为是由一小部分具有干细胞特性的细胞引发的,这些细胞包括自我更新、多能分化、肿瘤组织起始和对治疗的抗性。癌症干细胞(CSC)也已在神经胶质瘤中被鉴定出来,在神经胶质瘤中被命名为神经胶质瘤干细胞样细胞(GSLCs)或神经胶质瘤干细胞。在异种移植移植模型中,GSLC 会增殖肿瘤并促进肿瘤进展。GSLC 的肿瘤发生不仅取决于其自主增殖,还取决于与微环境成分的相互作用。在这些成分中,G 蛋白偶联趋化因子受体(GPCR)及其激动剂因其介导白细胞浸润、血管生成、肿瘤侵袭和转移的能力而引起了广泛关注。趋化因子 GPCR 广泛表达于肿瘤细胞和基质细胞,并识别肿瘤微环境中存在的激动剂。这些 GPCR 也被发现存在于包括 GSLC 在内的 CSC 中。在这篇简短的综述中,我们将总结趋化因子 GPCR 在 GSLC 中的功能、调节和信号转导的最新研究进展,希望能促进更好地理解神经胶质瘤进展的机制基础,并确定新的抗神经胶质瘤治疗的分子靶点。

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