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Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells.

白血病细胞上的硫酸乙酰肝素蛋白聚糖主要参与整合素触发及其介导的与内皮细胞的粘附。

基本信息

批准号：
07670550
负责人：
TANAKA Yoshiya
金额：
$ 1.54万
依托单位：
University of Occupational & Environmental Health (U.O.E.H.)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670550/
关键词：
Leukemia Chemokine Proteoglycan Integrin Adhesion Endothelium Metastasis

项目摘要

Leukocyte migration from ciculation into tissue depends on leukocyte integrin-mediated adhesion to endothelium, but integrins cannot function until activated. However, it remains to be understood how tumor cells adhere to endothelium and infiltrate into underlying tissue. We studied mechanisms of extravasation of leukemic cells using adult T cell leukemia (ALT) cells and report the following novel features of cell surface heparan sulfate proteoglycan on ATL cells in ATL cell adhesion to endothelium. (1) ATL cells adhere to endothelial cells through already activated integrins without exogenous stimulation. (2) Different from any other hematopoietic cells, ATL cells express a characteristic heparan sulfate capable of immobilizing heparin-binding chemokine macrophage inflammatory protein (MIP) -1beta, a potent T cell-integrin-trigger, produced by the cells themselves. (3) Competitive interruption of endogenous heparan sulfate proteoglycan-synthesis reduces cell surface MIP-1beta and prev … More ents ATL cells from integrin-mediated adhesion to endothelial cells of ICAM-1 triggered through G-protein. (4) The heparan sulfate proteoglycan on ATL cells characteristically consists of an 100 kDa unknown core protein and extremely weakly sulfated glycosaminoglycan, which has a potency to bind to distinctive heparin-binding cytokines.Thus, we here propose that leukemic cells adhere to endothelial cells through the adhesion cascade, similar to normal leukocyte, and that the cell surface heparan sulfate particularly on ATL cells is pivotally involved in chemokine-dependent autocrine stimulation of integrin-triggering by immobilizing the chemokine on them. This is the first study to explore the significance of interaction among heparan sulfate proteoglycan and heparin-binding cytokine for circulating tumor adhesion. Our finding would warrant further studies that different proteoglycan and cytokine might bring enormous flexibility to the process of leukemic cell infiltration and tumor metastasis and would introduce new pharmacological approaches to control them. Less

白细胞从结缔组织到组织的迁移依赖于白细胞整合素介导的内皮黏附，但整合素只有在被激活后才能发挥作用。然而，肿瘤细胞如何黏附于血管内皮细胞并向其下层组织渗透仍有待进一步了解。我们研究了成人T细胞白血病(ALT)细胞外渗白血病细胞的机制，并报道了ATL细胞表面硫酸乙酰肝素蛋白多糖在ATL细胞与内皮细胞黏附中的以下新特征。(1)ATL细胞通过已激活的整合素与内皮细胞黏附，无需外源性刺激。(2)与任何其他造血细胞不同，ATL细胞表达一种特有的硫酸肝素，能够固定肝素结合的趋化因子巨噬细胞炎性蛋白(MIP)-1β，这是一种由细胞本身产生的强大的T细胞整合素触发器。(3)竞争性阻断内源性硫酸乙酰肝素蛋白多糖合成减少细胞表面mip-1β和前病毒…更多的ATL细胞由整合素介导的与ICAM-1内皮细胞的黏附通过G蛋白触发。(4)ATL细胞表面的硫酸肝素蛋白多糖主要由100 kDa的未知核心蛋白和极弱的硫酸化糖胺多糖组成，具有与不同肝素结合的细胞因子结合的能力。因此，我们认为白血病细胞通过与正常白细胞类似的黏附级联与内皮细胞黏附，细胞表面的硫酸乙酰肝素尤其是ATL细胞表面的硫酸乙酰肝素通过将趋化因子固定在内皮细胞上而参与趋化因子依赖的整合素触发的自分泌刺激。这是首次探讨硫酸肝素蛋白多糖和肝素结合细胞因子之间的相互作用对循环肿瘤黏附的意义。我们的发现将值得进一步研究，即不同的蛋白多糖和细胞因子可能会给白血病细胞侵袭和肿瘤转移过程带来巨大的灵活性，并将引入新的药理学方法来控制它们。较少