Abstract
Heparanase is an endoglycosidase that degrades heparan sulfate, the main polysaccharide constituent of the extracellular matrix (ECM) and basement membrane. Expression of the heparanase gene is associated with the invasion and metastatic potential of a variety of tumor-derived cell types. However, the roles of heparanase in the regulation of gene expression and the subsequent cell function changes other than invasion are not clear. In the current study, we overexpressed the human heparanase gene in a human U251n glioma cell line. We found that heparanase-overexpression significantly increased cell invasion, proliferation, anchorage-independent colony formation and chemotactic migration towards fetal bovine serum (FBS)-supplied medium and stromal cell-derived factor-1 (SDF-1). These phenotypic appearances were accompanied by enhanced protein kinase B (AKT) phosphorylation. Focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1 (ERK1) signaling were not altered by heparanase-overexpression. These results indicate that heparanase has pleiotropic effects on tumor cells.
Highlights
Tumor cell invasion and metastatic spread depend on the ability of cancer cells to invade tissue barriers by degrading extracellular matrix (ECM) and basement membrane structures [1,2]
We demonstrate that heparanase overexpression in stably transfected human U251n glioma cells results in a marked increase of cell chemotactic migration toward fetal bovine serum (FBS)-supplied medium and stromal cell-derived factor-1 (SDF-1)
Heparanase increases U251n cell invasion To understand the role of heparanase on the regulation of cell function, the full length human heparanase gene was stably transfected into U251n cells
Summary
Tumor cell invasion and metastatic spread depend on the ability of cancer cells to invade tissue barriers by degrading extracellular matrix (ECM) and basement membrane structures [1,2]. The primary components of the basement membrane and ECM are structural proteins, such as collagen IV, laminin, fibronectin, and heparan sulfate proteoglycans (HSPGs). Heparan sulfate (HS) is a glycosaminoglycon (GAG) chain present in HSPGs [3]. HS chains interact through specific attachment sites with the main protein components of basement membrane and ECM. Heparanase is a mammalian endo-β-D-glucuronidase responsible for HS degradation [4,5,6,7]. Heparanase activity may play an important role in fundamental biological processes associated with ECM remodeling and cell invasion [8,9]. Increased expression of heparanase (page number not for citation purposes)
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