Heparanase mediates cell adhesion independent of its enzymatic activity

Orit Goldshmidt, Eyal Zcharia, Miriam Cohen, Helena Aingorn, Irit Cohen, Liat Nadav, Ben Zion Katz, Benjamin Geiger, Israel Vlodavsky

Research output: Contribution to journalArticlepeer-review

Abstract

Heparanase is an endo-β-D-glucuroni-dase 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, 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.

Original languageEnglish
Pages (from-to)1015-1025
Number of pages11
JournalFASEB Journal
Volume17
Issue number9
DOIs
StatePublished - Jun 2003
Externally publishedYes

Keywords

  • Extracellular matrix
  • Heparan sulfate
  • Invasion

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