Functional Characterization of A Novel Glycosaminoglycan Binding Peptide on Tumor Targeting and Suppression

• Main Authors: Tsai, Kang-Chiao, 蔡岡橋
• Other Authors: Chang, Dah-Tsyr
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/p2kej4

碩士 === 國立清華大學 === 分子與細胞生物研究所 === 102 === Cell surface glycosaminoglycans (GAGs), which play diverse roles in cancer progression to regulate proliferation, adhesion, migration, and angiogenesis, interact with molecules including chemokines, thrombins and growth factors. We have recently identified a non-cytotoxic and sulfated GAG-binding peptide (GBP) derived from core heparan sulfate binding motif of human eosinophil cationic protein (hECP). Recombinant enhanced green fluorescent protein-fused GBP (eGFP-GBP) bound to mouse colon (CT-26) and human lung (A549) epithelial cancer cells in a dose-dependent manner determined by enzyme-linked immunosorbent assay (ELISA). Through in vivo tissue targeting experiment carried out in subcutaneous CT-26 syngeneic tumor mouse model (Balb/c), eGFP-GBP signals were detected in subcutaneous CT-26 tumor site, liver and kidney by immunohistochemistry (IHC) staining. In addition, GBP-conjugated magnetic nanoparticle (MNP-GBP) signals were also observed in subcutaneous CT-26 tumor site using Prussian blue staining. Furthermore, in vitro migration assay indicated that the migration activities of CT-26 and A549 cell and human umbilical vein endothelial cell (HUVEC) were significantly inhibited upon treatment of GBP. Moreover, GBP inhibited the growth of subintestinal vessel (SIV) in zebrafish and suppressed tumor growth in subcutaneous A549 xenogeneic tumor mouse model (SCID). Taken together, this study demonstrated that GBP possessed not only epithelial tumor targeting activity but also anti-migration and anti-angiogenesis activities. Thus, further development of GBP as a reagent for application in translational medicine is feasible.