Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.
Prog Mol Biol Transl Sci. 2010;95:113-58. doi: 10.1016/B978-0-12-385071-3.00006-X.
In this chapter we provide an overview of stem cells in normal tissues as well as in many different types of cancers. All tissues in the body are derived from organ-specific stem cells that retain the ability to self-renew and differentiate into specific cell types. The cancer stem cell hypothesis suggests that tumors arise from cell populations with dysregulated self-renewal. This may be tissue stem cells or more differentiated cells that acquire self-renewal capabilities. In addition, we outline some useful assays for purification and isolation of cancer stem cells including the dye exclusion side population assay, flow cytometry sorting techniques for identification of putative cancer stem cell markers, tumorspheres assay, aldehyde dehydrogenase activity assay, PKH, and other membrane staining used to label the cancer stem cells, as well as in vivo xenograft transplantation assays. We also examine some of the cell signaling pathways that regulate stem cell self-renewal including the Notch, Hedgehog, HER2/PI3K/Akt/PTEN, and p53 pathways. We also review information demonstrating the involvement of the microenvironment or stem cell niche and its effects on the growth and maintenance of cancer stem cells. Finally, we highlight the therapeutic implications of targeting stem cells by inhibiting these pathways for the treatment and prevention of cancer.
在本章中，我们提供了对正常组织以及许多不同类型癌症中的干细胞的概述。 体内所有组织均源自具有自我更新能力并能分化为特定细胞类型的器官特异性干细胞。 癌症干细胞假说表明，肿瘤源自自我更新失调的细胞群。 这些细胞可能是组织干细胞或获得自我更新能力的更分化的细胞。 此外，我们概述了一些用于纯化和分离癌症干细胞的有用方法，包括染料排斥性侧群测定法，用于鉴定假定的癌症干细胞标记物的流式细胞术分选技术，肿瘤球体测定法，醛脱氢酶活性测定法，PKH 和其他用于标记癌症干细胞的膜染色，以及体内异种移植移植测定法。 我们还研究了一些调节干细胞自我更新的细胞信号通路，包括 Notch，Hedgehog，HER2 / PI3K / Akt / PTEN 和 p53 通路。 我们还回顾了有关微环境或干细胞生态位及其对癌症干细胞生长和维持的影响的信息。 最后，我们强调了通过抑制这些途径靶向干细胞来治疗和预防癌症的治疗意义。
