Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer.
Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer.
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DOI：
10.3389/fimmu.2015.00201
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发表时间：
2015
影响因子：
7.3
通讯作者：
Ghatak S
中科院分区：
文献类型：
--
作者：
Misra S;Hascall VC;Markwald RR;Ghatak S
糖胺聚糖透明质酸（HA）是细胞外基质的主要成分，其细胞表面受体在细胞增殖、迁移和侵袭中起着关键作用，这是炎症和癌症进展所必需的。CD44和ha介导运动受体（receptor for HA-mediated motility， RHAMM）是两种主要的ha受体，它们在人和鼠炎症和肿瘤细胞中的生物学功能已经得到了全面的研究。HA最初被认为只是结缔组织的一种惰性成分，但现在被认为是一种“动态”分子，通过快速代谢在许多组织中不断周转，涉及各种大小的HA分子：高分子量HA (HMW HA)，低分子量HA和低聚糖。HA与CD44和RHAMM相互作用启动的细胞内信号通路导致炎症和致瘤反应是复杂的。有趣的是，这些分子在炎症和肿瘤发生中具有双重功能。例如，CD44的存在参与关节炎的发生，而在关节炎小鼠模型中，由于基因缺失导致的CD44缺失增加而不是减少了疾病的严重程度。CD44在癌症的发生和发展中也存在类似的双重功能。RHAMM过表达通常与癌症进展有关，而RHAMM的缺失则与恶性周围神经鞘肿瘤的生长有关。HA可以类似地执行双重功能。丰富的HMW HA可以促进恶性细胞的增殖和癌症的发展，而HA- cd44信号拮抗剂通过干扰HMW HA- cd44相互作用，在体外和体内抑制肿瘤细胞的生长。本文综述了HA与CD44和RHAMM相互作用在炎症反应和肿瘤发生/进展中的作用，以及如何在啮齿动物和人类疾病中开发出阻断这些关键炎症/致瘤过程的治疗策略。
The glycosaminoglycan hyaluronan (HA), a major component of extracellular matrices, and cell surface receptors of HA have been proposed to have pivotal roles in cell proliferation, migration, and invasion, which are necessary for inflammation and cancer progression. CD44 and receptor for HA-mediated motility (RHAMM) are the two main HA-receptors whose biological functions in human and murine inflammations and tumor cells have been investigated comprehensively. HA was initially considered to be only an inert component of connective tissues, but is now known as a “dynamic” molecule with a constant turnover in many tissues through rapid metabolism that involves HA molecules of various sizes: high molecular weight HA (HMW HA), low molecular weight HA, and oligosaccharides. The intracellular signaling pathways initiated by HA interactions with CD44 and RHAMM that lead to inflammatory and tumorigenic responses are complex. Interestingly, these molecules have dual functions in inflammations and tumorigenesis. For example, the presence of CD44 is involved in initiation of arthritis, while the absence of CD44 by genetic deletion in an arthritis mouse model increases rather than decreases disease severity. Similar dual functions of CD44 exist in initiation and progression of cancer. RHAMM overexpression is most commonly linked to cancer progression, whereas loss of RHAMM is associated with malignant peripheral nerve sheath tumor growth. HA may similarly perform dual functions. An abundance of HMW HA can promote malignant cell proliferation and development of cancer, whereas antagonists to HA-CD44 signaling inhibit tumor cell growth in vitro and in vivo by interfering with HMW HA-CD44 interaction. This review describes the roles of HA interactions with CD44 and RHAMM in inflammatory responses and tumor development/progression, and how therapeutic strategies that block these key inflammatory/tumorigenic processes may be developed in rodent and human diseases.
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DOI：
10.1083/jcb.131.6.1623
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bennett KL;Modrell B;Greenfield B;Bartolazzi A;Stamenkovic I;Peach R;Jackson DG;Spring F;Aruffo A
通讯作者：
Aruffo A
影响因子：
4
作者：
Acharya, Pinak S.;Majumdar, Sonali;Pure, Ellen
通讯作者：
Pure, Ellen
影响因子：
4.8
作者：
Bourguignon, Lilly Y. W.;Spevak, Christina C.;Gilad, Eli
通讯作者：
Gilad, Eli
影响因子：
10.8
作者：
Bookbinder, L. H.;Hofer, A.;Frost, G. I.
通讯作者：
Frost, G. I.
影响因子：
4.8
作者：
Bourguignon, LYW;Singleton, PA;Diedrich, F
通讯作者：
Diedrich, F