Heparanase mediates cell adhesion independent of its enzymatic activity

ABSTRACT Heparanase is an endo‐β‐D‐glucuronidase that cleaves heparan sulfate and is implicated in diverse physiological and pathological processes. In this study we report on a novel direct involvement of heparanase in cell adhesion. We demonstrate that expression of heparanase in nonadherent lymph...

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Published in:The FASEB journal 2003-06, Vol.17 (9), p.1015-1025
Main Authors: GOLDSHMIDT, ORIT, ZCHARIA, EYAL, COHEN, MIRIAM, AINGORN, HELENA, COHEN, IRIT, NADAV, LIAT, KATZ, BEN-ZION, GEIGER, BENJAMIN, VLODAVSKY, ISRAEL
Format: Article
Language:English
Subjects:
Animals
Cell Adhesion
Cell Membrane - enzymology
Cell Size
Cells, Cultured
Cytoskeletal Proteins - metabolism
Endothelium - physiology
extracellular matrix
Extracellular Matrix - metabolism
Glucuronidase - antagonists & inhibitors
Glucuronidase - metabolism
Glucuronidase - physiology
heparan sulfate
invasion
Lymphoma - enzymology
Lymphoma - pathology
Mice
Neoplasm Invasiveness
Oligopeptides - pharmacology
Paxillin
Phosphoproteins - metabolism
Phosphorylation
Tumor Cells, Cultured
Tyrosine - metabolism
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Summary:ABSTRACT Heparanase is an endo‐β‐D‐glucuronidase that cleaves heparan sulfate and is implicated in diverse physiological and pathological processes. In this study we report on a novel direct involvement of heparanase in cell adhesion. We demonstrate that expression of heparanase in nonadherent lymphoma cells induces early stages of cell adhesion, provided that the enzyme is expressed on the cell surface. Heparanasemediated cell adhesion to extracellular matrix (ECM) results in integrin‐dependent cell spreading, tyrosine phosphorylation of paxillin, and reorganization of the actin cytoskeleton. The surface‐bound enzyme also augments cell invasion through a reconstituted basement membrane. Cell adhesion was augmented by cell surface heparanase regardless of whether the cells were transfected with active or point mutated inactive enzyme, indicating that heparanase functions as an adhesion molecule independent of its endoglycosidase activity. The combined feature of heparanase as an ECM‐degrading enzyme and a cell adhesion molecule emphasizes its significance in processes involving cell adhesion, migration, and invasion, including embryonic development, neovascularization, and cancer metastasis.— Goldshmidt, O., Zcharia, E., Cohen, M., Aingorn, H., Cohen, I., Nadav, L., Katz, B.‐Z., Geiger, B., Vlodavsky, I. Heparanase mediates cell adhesion independent of its enzymatic activity. FASEB J. 17, 1015–1025 (2003)
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.02-0773com