Competitive Inhibition of Biotin-TSG-6-ΔHep-Fc and Biotin-HABP Binding to Immobilized HA using HA , Chondroitin Sulfate A , Chondroitin Sulfate C and Heparin Solutions

Hyaluronan (HA) is a linear glycosaminoglycan (GAG) composed of repeating disaccharide units of glucuronic acid β1-3/N-acetylglucosamine β1-4. HA is ubiquitously distributed in the extracellular and pericellular matrices of tissues and can sometimes be found inside cells (Evanko and Wight 1999; Hascall et al. 2004; Toole 2004). In mammals, the dynamic turnover of HA is a finely tuned equilibrium of biosynthesis by three membranebound HA synthases and catabolism by several hyaluronidases (Weigel et al. 1997; Itano and Kimata 2002; Stern et al. 2005; Jadin et al. 2012). This controlled balance is frequently disturbed in malignancies, in which up-regulation of HA production has been associated with more aggressive and invasive behavior (Itano et al. 2008; Toole 2009; Kultti et al. 2012). Therefore, targeting tumor-associated HA has generated promising results as a new approach to cancer therapy. A pegylated recombinant human hyaluronidase (PEGPH20) has been shown to deplete tumor HA and lead to increased tumor perfusion, thereby enhancing the activity of anticancer agents in preclinical models (Thompson 540176 JHCXXX10.1369/0022155414540176Jadin et al.Characterization of a Recombinant HABP research-article2014