Premium
The heparanase/syndecan‐1 axis in cancer: mechanisms and therapies
Author(s) -
Ramani Vishnu C.,
Purushothaman Anurag,
Stewart Mark D.,
Thompson Camilla A.,
Vlodavsky Israel,
Au Jessie LS.,
Sanderson Ralph D.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12168
Subject(s) - heparanase , syndecan 1 , heparan sulfate , cancer research , angiogenesis , fibroblast growth factor , proteoglycan , cancer cell , transmembrane protein , cancer , microbiology and biotechnology , biology , cell , medicine , heparin , extracellular matrix , biochemistry , receptor
Heparanase is an endoglucuronidase that cleaves heparan sulfate chains of proteoglycans. In many malignancies, high heparanase expression and activity correlate with an aggressive tumour phenotype. A major consequence of heparanase action in cancer is a robust up‐regulation of growth factor expression and increased shedding of syndecan‐1 (a transmembrane heparan sulfate proteoglycan). Substantial evidence indicates that heparanase and syndecan‐1 work together to drive growth factor signalling and regulate cell behaviours that enhance tumour growth, dissemination, angiogenesis and osteolysis. Preclinical and clinical studies have demonstrated that therapies targeting the heparanase/syndecan‐1 axis hold promise for blocking the aggressive behaviour of cancer.