PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.

ABSTRACT: PG545 is a clinically relevant heparan sulfate (HS) mimetic which, in addition to possessing anti-angiogenic properties, also acts as a heparanase inhibitor which may differentiate its mechanism(s) of action from approved angiogenesis inhibitors. The degradation of HS by heparanase has been strongly implicated in cell dissemination and the metastatic process. Thus, the anti-metastatic activity of PG545 has been linked to the enzymatic function of heparanase - the only endoglycosidase known to cleave HS, an important component of the extracellular matrix (ECM) which represents a potential avenue for therapeutic intervention for certain metastatic cancer indications. Recent concerns raised about the paucity of overall survival as an endpoint in mouse models of clinically relevant metastasis

SUBMITTER: Hammond E 

PROVIDER: S-EPMC3530599 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature