Murine macrophage heparanase: inhibition and comparison with metastatic tumor cells
Circulating macrophages and metastatic tumor cells can penetrate the vascular endothelium and migrate from the circulatory system to extravascular compartments. Both activated murine macrophages and different metastatic tumor cells attach, invade, and penetrate confluent vascular endothelial cell monolayer in vitro, by degrading heparan sulfate proteoglycans in the subendothelial extracellular matrix. The sensitivity of the enzymes from the various sources degrading the heparan sulfate proteoglycan was challenged and compared by a series of inhibitors. Activated macrophages demonstrate a heparanase with an endoglycosidase activity that cleaves from the (/sup 35/S)O/sub 4//sup -/-labeled heparan sulfate proteoglycans of the extracellular matrix 10 kDa glycosaminoglycan fragments. The degradation of (/sup 35/S)O/sub 4//sup -/-labeled extracellular matrix proteoglycans by the macrophages' heparanase is significantly inhibited in the presence of heparan sulfate (10..mu..g/ml), arteparon (10..mu..g/ml), and heparin at a concentration of 3 ..mu..g/ml. Degradation of this heparan sulfate proteoglycan is a two-step sequential process involving protease activity followed by heparanase activity. B16-BL6 metastatic melanoma cell heparanase, which is also a cell-associated enzyme, was inhibited by heparin to the same extent as the macrophage haparanase. On the other hand, heparanase of the highly metastatic variant (ESb) of a methylcholanthrene-induced T lymphoma, which is an extracellular enzyme released by the cells to the incubation medium, was more sensitive to heparin and arteparon than the macrophages' heparanase. These results may indicate the potential use of heparin or other glycosaminoglycans as specific and differential inhibitors for the formation in certain cases of blood-borne tumor metastasis.
- Research Organization:
- Tel-Aviv Univ., Tel Hashomer, Israel
- OSTI ID:
- 6525615
- Journal Information:
- J. Cell. Physiol.; (United States), Vol. 130:1
- Country of Publication:
- United States
- Language:
- English
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GLUCOPROTEINS
BIODEGRADATION
LABELLED COMPOUNDS
MACROPHAGES
BIOCHEMISTRY
METASTASES
INHIBITION
TUMOR CELLS
ENDOTHELIUM
ENZYME ACTIVITY
ENZYME INHIBITORS
HEPARIN
MICE
PEPTIDE HYDROLASES
SODIUM COMPOUNDS
SULFATES
SULFUR 35
ALKALI METAL COMPOUNDS
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CHEMICAL REACTIONS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DRUGS
ENZYMES
EVEN-ODD NUCLEI
HEMATOLOGIC AGENTS
HYDROLASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MUCOPOLYSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PHAGOCYTES
POLYSACCHARIDES
PROTEINS
RADIOISOTOPES
RODENTS
SACCHARIDES
SOMATIC CELLS
SULFUR COMPOUNDS
SULFUR ISOTOPES
TISSUES
VERTEBRATES
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