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

白细胞从循环到组织的迁移取决于白细胞整合素介导的与内皮的粘附，但整合素在激活之前无法发挥作用。然而，肿瘤细胞如何粘附到内皮并渗透到底层组织中仍有待了解。我们研究了白血病细胞外渗的机制。使用成人T细胞白血病（ALT）细胞，报告了ATL细胞中ATL细胞表面硫酸乙酰肝素蛋白多糖的以下新特征(1) ATL 细胞在没有外源刺激的情况下通过已激活的整合素粘附于内皮细胞。 (2) 与任何其他造血细胞不同，ATL 细胞表达能够固定肝素结合趋化因子巨噬细胞炎症蛋白 (MIP) 的特征性硫酸乙酰肝素。 ) ) -1beta，一种有效的 T 细胞整合素触发剂，由细胞本身产生 (3) 内源性竞争性中断。硫酸乙酰肝素蛋白聚糖的合成可减少细胞表面 MIP-1β，并阻止 ATL 细胞通过 G 蛋白 100 kDa 未知核心蛋白和极弱的硫酸化糖胺聚糖触发整合素介导的 ICAM-1 粘附。效力与独特的肝素结合细胞因子结合。因此，我们在这里提出，白血病细胞通过粘附级联粘附到内皮细胞，类似于正常白细胞，并且细胞表面硫酸乙酰肝素，特别是 ATL 细胞上的硫酸乙酰肝素，在趋化因子依赖性自分泌刺激中起着关键作用通过将趋化因子固定在其上来触发整合素这是第一个探讨硫酸乙酰肝素之间相互作用的意义的研究。我们的发现需要进一步研究，不同的蛋白聚糖和细胞因子可能为白血病细胞浸润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。