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

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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