Differentiating human leukemia cells express heparanase that degrades heparan sulfate in subendothelial extracellular matrix.
Human promyelocytic (HL-60) and monoblast-like (U-937) leukemia cell lines were tested for expression of an endoglycosidase (heparanase) capable of degrading heparan sulfate (HS) side chains in the subendothelial extracellular matrix (ECM). Heparanase activity has been previously shown to be expressed by activated lymphocytes and macrophages and by highly metastatic tumor cells, in correlation with their ability to invade blood vessels and extracellular matrices. Incubation of HL-60 and U-937 cells with sulfate-labeled ECM in the presence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) resulted in heparanase-mediated release of heparan sulfate degradation products. This degradation was inhibited by heparin, stimulated by plasminogen and not expressed by cells treated with retinoic acid or dimethylsulfoxide and undergoing neutrophilic differentiation. Heparanase activity was not detected in media conditioned by HL-60 and U-937 cells but was found in their cell lysates, regardless of whether or not the cells were exposed to TPA. These findings imply that TPA-induced differentiation of human myeloid leukemic cells to macrophage-like cells, but not to neutrophilic granulocytes, is associated with expression on the cell surface of a preformed heparanase activity. The enzyme may serve as a marker for human cell differentiation into macrophages, allowing the differentiating cells to traverse the vascular compartment and reach their target sites.
Yahalom
J
J
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Fibach
E
E
Bar-Tana
R
R
Fuks
Z
Z
Vlodavsky
I
I
D002460:Cell Line; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology*; D005966:Glucuronidase; D006025:Glycosaminoglycans / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology*; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology*; D008970:Molecular Weight; D010958:Plasminogen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099175:Heparanase
D005966:Glucuronidase; D006025:Glycosaminoglycans; D006026:Glycoside Hydrolases; D006497:Heparan Sulfate; D010958:Plasminogen; D013755:Tetradecanoylphorbol Acetate; D000099175:Heparanase