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Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling.通过干扰 CD44v6 信号抑制胰腺癌模型中的肿瘤生长和转移。
Gastroenterology. 2016 Feb;150(2):513-25.e10. doi: 10.1053/j.gastro.2015.10.020. Epub 2015 Oct 24.
2
CD44 is a multidomain signaling platform that integrates extracellular matrix cues with growth factor and cytokine signals.CD44 是一个具有多种结构域的信号平台，它整合了细胞外基质线索与生长因子和细胞因子信号。
Adv Cancer Res. 2014;123:231-54. doi: 10.1016/B978-0-12-800092-2.00009-5.
3
CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.CD44v6 是驱动结肠癌转移的组成性和重编程癌症干细胞的标志物。
Cell Stem Cell. 2014 Mar 6;14(3):342-56. doi: 10.1016/j.stem.2014.01.009.
4
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Biomaterials. 2014 Feb;35(5):1411-9. doi: 10.1016/j.biomaterials.2013.11.011. Epub 2013 Nov 22.
5
Opposing effects of high- and low-molecular weight hyaluronan on CXCL12-induced CXCR4 signaling depend on CD44.高分子量和低分子量透明质酸对 CXCL12 诱导的 CXCR4 信号的相反作用取决于 CD44。
Cell Death Dis. 2013 Oct 3;4(10):e819. doi: 10.1038/cddis.2013.364.
6
Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis.抑制 Stabilin-2 可提高循环透明质酸水平并防止肿瘤转移。
Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4263-8. doi: 10.1073/pnas.1117560109. Epub 2012 Feb 27.
7
The interaction between CD44 on tumour cells and hyaluronan under physiologic flow conditions: implications for metastasis formation.肿瘤细胞表面的 CD44 与透明质酸在生理流动条件下的相互作用：对转移形成的影响。
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8
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Shear stress regulates adhesion and rolling of CD44+ leukemic and hematopoietic progenitor cells on hyaluronan.切应力调节 CD44+白血病和造血祖细胞在透明质酸上的黏附和滚动。
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CD44 介导 HepG2Iso 上皮癌细胞在透明质酸上的黏附-解离激活滚动。

CD44 mediates the catch-bond activated rolling of HEPG2Iso epithelial cancer cells on hyaluronan.

机构信息

a Department of Medicine V , University Hospital Heidelberg , Heidelberg , Germany.

b Analytical Chemistry - Biointerfaces, Ruhr-University Bochum , Bochum , Germany.

出版信息

Cell Adh Migr. 2017 Sep 3;11(5-6):476-487. doi: 10.1080/19336918.2016.1260809. Epub 2017 Feb 1.

DOI:10.1080/19336918.2016.1260809
PMID:27874296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5810759/
Abstract

The attachment of cancer cells to the endothelium is an essential step during metastatic dissemination. The cell surface receptor CD44 is capable of binding to hyaluronan (HA) produced by tumor cells and by cells of the tumor microenvironment, including blood endothelial cells. Here, we investigated the role of CD44 in the interaction between the liver cancer cell line HepG2Iso and HA surfaces. The rolling interaction was quantitatively analyzed using a microfluidic shear force setup. It was found that rolling of the liver cancer cells on HA depends on CD44, which mediates a catch-bond interaction and thus a flow-induced rolling of the cells. Reduction of CD44 expression by means of siRNA, inhibition of the interaction of CD44 with HA by antibody blocking, and treatment with low molecular weight HA inhibited liver cancer cell rolling on HA-coated surfaces. The results not only clearly show the dependency of the shear-induced catch-bond interaction of HepG2Iso cells on CD44 and HA, but also for the first time demonstrate CD44-mediated rolling for epithelium-derived cells that are typically adherent.

摘要

癌细胞与内皮细胞的附着是转移扩散过程中的一个重要步骤。细胞表面受体 CD44 能够与肿瘤细胞和肿瘤微环境中的细胞（包括血液内皮细胞）产生的透明质酸 (HA) 结合。在这里，我们研究了 CD44 在肝癌细胞系 HepG2Iso 与 HA 表面相互作用中的作用。使用微流体力设置定量分析了滚动相互作用。结果发现，肝癌细胞在 HA 上的滚动依赖于 CD44，CD44 介导了一个捕获键相互作用，从而诱导细胞的流动滚动。通过 siRNA 减少 CD44 的表达、抗体阻断 CD44 与 HA 的相互作用以及用低分子量 HA 处理，抑制了肝癌细胞在 HA 涂层表面上的滚动。这些结果不仅清楚地表明了 HepG2Iso 细胞的剪切诱导捕获键相互作用对 CD44 和 HA 的依赖性，而且首次证明了 CD44 介导的通常是附着的上皮细胞的滚动。