Abstract 3035: Functional roles of HS6ST3 in human breast cancer in vitro

Abstract

Abstract Introduction: Heparan sulfate is a sulfated polysaccharide that is found on the cell surface and extracellular matrix of all human cells. It interacts with a variety of proteins and is thus involved in numerous biological processes such as growth and development. Heparan sulfate's function critically depends on the number and the position of sulfate groups, which modulate the binding sites for proteins such as growth factors, cytokines, receptors, enzymes, and inhibitors. However, little is known about their roles both in vitro and in vivo. Alterations in heparan sulfation may be associated with pathologic conditions such as cancer. Heparan sulfate 6-O-sulfotransferases (HS6STs) catalyze the transfer of sulfate groups to the carbon 6 position in heparan sulfate. Three isoforms of these enzymes have been discovered in humans. Recently, several studies have proposed that dysregulation of 6-O-sulfation patterns may be involved in carcinogenesis. This study aimed to analyze the functional role of HS6ST3 in T47D breast cancer cell line. Procedures: HS6ST3 was silenced using siRNA by more than 85%. Functional studies such as proliferation, cell cycle, apoptosis, adhesion and migration assays were then performed. Results: The study demonstrated that silencing HS6ST3 in T47D breast cancer cell line enhanced apoptosis and cellular adhesion; and diminished proliferation with cell cycle arrest at G0/G1. Taken together the results demonstrated that silencing HS6ST3 decreased the tumoral progression in breast cancer. Conclusions: This could be happen through alteration of heparan sulfate interactions with ligands such as growth factors. HS6ST3 could be used not only as a valuable biomarker for diagnostic and prognostic purposes but in cancer gene therapy in near future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3035. doi:10.1158/1538-7445.AM2011-3035