title: Inhibition of metastatic tumor formation in vivo by a bacteriophage display-derived galectin-3 targeting peptide.
abstract: Galectin-3 (gal-3) is involved in the metastatic cascade and interacts with the cancer-associated carbohydrate, Thomsen-Freidenreich (TF) antigen during early stages of metastatic adhesion and tumor formation. Our laboratory previously utilized bacteriophage display to select a peptide, G3-C12, with high specificity and affinity for gal-3 that was able to inhibit cancer cell adhesion. We hypothesized that G3-C12 would inhibit TF/gal-3 and gal-3/gal-3 interactions in vitro and in vivo and would moderate early steps of the metastatic cascade leading to reduced carcinogenesis in vivo. To test this, adhesion of multiple breast carcinoma cell lines to purified gal-3 and a TF-mimic was measured in the presence/absence of G3-C12 resulting in an average reduction of cellular adhesion by 50 and 59 %, respectively. Sensitive optical imaging experiments were utilized to monitor the fate of intravenously injected MDA-MB-231 human breast carcinoma cells expressing luciferase into athymic nude mice in the presence/absence of G3-C12 in vivo. Intravenous administration of G3-C12 reduced lung colonization of MDA-MB-231-luciferase cells within mice by 72 % when compared to saline, whereas, control peptide treatments resulted in no significant reduction of colonization. Histologic examination of excised lung tissue, at day 70, revealed that mice treated with G3-C12 possessed 4.63 ± 3.07 tumors compared to 14.13 ± 3.56 tumors within mice treated with saline. Also, within both saline and control peptide treatment groups, 37 % of mouse lungs contained tumor thrombi, compared to 0 % within the G3-C12 treatment group. This study demonstrated that G3-C12 significantly reduced metastatic cell deposition and consequent outgrowth within vasculature of mice.
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Newton-Northup
authors.forename: Marie T
authors.initials: MT
authors.lastname: Dickerson
authors.forename: Lixin
authors.initials: L
authors.lastname: Ma
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Besch-Williford
authors.forename: Susan L
authors.initials: SL
authors.lastname: Deutscher
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D001435:Bacteriophages / Q000276:immunology*; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D005260:Female; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000627:therapeutic use*; D019151:Peptide Library; D014407:Tumor Cells, Cultured
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D037502:Galectin 3; D010446:Peptide Fragments; D019151:Peptide Library; C016467:Thomsen-Friedenreich antigen; D008156:Luciferases