Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin triggering and its mediated adhesion to endothelial cells.
Leukocyte migration from circulation 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 (ATL) cells and report the following novel features of cell surface heparan sulfate proteoglycan on ATL cells in ATL cell adhesion to endothelium: ATL cells adhere to endothelial cells through already activated integrins without exogenous stimulation; different from any other hematopoietic cells, ATL cells express a characteristic heparan sulfate capable of immobilizing heparin-binding chemokine macrophage inflammatory protein (MIP)-1 beta, a potent T cell integrin trigger, produced by the cells themselves; competitive interruption of endogenous heparan sulfate proteoglycan synthesis reduces cell surface MIP-1 beta and prevents ATL cells from integrin-mediated adhesion to endothelial cells or intercellular adhesion molecule-1 triggered through G-protein. We 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.
Tanaka
Y
Y
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Kimata
K
K
Wake
A
A
Mine
S
S
Morimoto
I
I
Yamakawa
N
N
Habuchi
H
H
Ashikari
S
S
Yamamoto
H
H
Sakurai
K
K
Yoshida
K
K
Suzuki
S
S
Eto
S
S
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D054407:Chemokine CCL4; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006027:Glycosides / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D015461:Leukemia, Prolymphocytic, T-Cell / Q000378:metabolism; D015458:Leukemia, T-Cell / Q000378:metabolism*; D017254:Leukemic Infiltration; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008954:Models, Biological; D009362:Neoplasm Metastasis; D010641:Phenotype; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured
D054407:Chemokine CCL4; D006027:Glycosides; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D019402:Macrophage Inflammatory Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C010807:xylosides