Department of Environmental Health, College of Medicine, University of Cincinnati, OH 45267, USA.
Exp Biol Med (Maywood). 2013 Mar;238(3):324-38. doi: 10.1177/1535370213480714.
The stem cell niche provides a regulatory microenvironment for cells as diverse as totipotent embryonic stem cells to cancer stem cells (CSCs) which exhibit stem cell-like characteristics and have the capability of regenerating the bulk of tumor cells while maintaining self-renewal potential. The transmembrane glycoprotein CD44 is a common component of the stem cell niche and exists as a standard isoform (CD44s) and a range of variant isoforms (CD44v) generated though alternative splicing. CD44 modulates signal transduction through post-translational modifications as well as interactions with hyaluronan, extracellular matrix molecules and growth factors and their cognate receptor tyrosine kinases. While the function of CD44 in hematopoietic stem cells has been studied in considerable detail, our knowledge of CD44 function in tissue-derived stem cell niches remains limited. Here we review CD44s and CD44v in both hematopoietic and tissue-derived stem cell niches, focusing on their roles in regulating stem cell behavior including self-renewal and differentiation in addition to cell-matrix interactions and signal transduction during cell migration and tumor progression. Determining the role of CD44 and CD44v in normal stem cell, CSC and (pre)metastatic niches and elucidating their unique functions could provide tools and therapeutic strategies for treating diseases as diverse as fibrosis during injury repair to cancer progression.
干细胞龛为各种细胞提供了一个调节微环境，包括全能胚胎干细胞和癌症干细胞（CSC），CSC 表现出干细胞样特征，具有再生肿瘤细胞大部分的能力，同时保持自我更新的潜力。跨膜糖蛋白 CD44 是干细胞龛的一个常见组成部分，存在标准同工型（CD44s）和一系列通过选择性剪接产生的变体同工型（CD44v）。CD44 通过翻译后修饰以及与透明质酸、细胞外基质分子和生长因子及其同源受体酪氨酸激酶的相互作用来调节信号转导。虽然 CD44 在造血干细胞中的功能已经得到了相当详细的研究，但我们对组织来源的干细胞龛中 CD44 功能的了解仍然有限。在这里，我们综述了造血和组织来源的干细胞龛中的 CD44s 和 CD44v，重点讨论了它们在调节干细胞行为（包括自我更新和分化）中的作用，以及在细胞迁移和肿瘤进展过程中的细胞-基质相互作用和信号转导。确定 CD44 和 CD44v 在正常干细胞、CSC 和（前）转移龛中的作用，并阐明其独特功能，可为治疗各种疾病提供工具和治疗策略，从损伤修复到癌症进展的纤维化。
