pg-545 and Colonic-Polyps

Heparanase activity is highly implicated in cellular invasion and tumor metastasis, a consequence of cleavage of heparan sulfate and remodeling of the extracellular matrix underlying epithelial and endothelial cells. Heparanase expression is rare in normal epithelia, but is often induced in tumors, associated with increased tumor metastasis and poor prognosis. In addition, heparanase induction promotes tumor growth, but the molecular mechanism that underlines tumor expansion by heparanase is still incompletely understood. Here, we provide evidence that heparanase down regulates the expression of p21 (WAF1/CIP1), a cyclin-dependent kinase inhibitor that attenuates the cell cycle. Notably, a reciprocal effect was noted for PG545, a potent heparanase inhibitor. This compound efficiently reduced cell proliferation, colony formation, and tumor xenograft growth, associating with a marked increase in p21 expression. Utilizing the APC Min

Topics: Animals; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Colonic Neoplasms; Colonic Polyps; Cyclin-Dependent Kinase Inhibitor p21; Disease Models, Animal; Down-Regulation; Enzyme Activation; Gene Expression Regulation, Neoplastic; Glucuronidase; Humans; Mice; Mice, Knockout; NF-kappa B; Saponins; Signal Transduction; Toll-Like Receptors; Xenograft Model Antitumor Assays