Heparanase mediates cell adhesion independent of its enzymatic activity.
Heparanase is an endo-beta-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. Heparanase-mediated 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
Orit
O
Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel.
Zcharia
Eyal
E
Cohen
Miriam
M
Aingorn
Helena
H
Cohen
Irit
I
Nadav
Liat
L
Katz
Ben-Zion
BZ
Geiger
Benjamin
B
Vlodavsky
Israel
I
D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000201:enzymology; D048429:Cell Size; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004727:Endothelium / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008223:Lymphoma / Q000201:enzymology / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009842:Oligopeptides / Q000494:pharmacology; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D000099175:Heparanase
D003598:Cytoskeletal Proteins; D005966:Glucuronidase; D009842:Oligopeptides; D051419:Paxillin; D010750:Phosphoproteins; D014443:Tyrosine; D000099175:Heparanase; C496062:Pxn protein, mouse; C047981:arginyl-glycyl-aspartic acid