title: Optical imaging of MMP expression and cancer progression in an inflammation-induced colon cancer model.
abstract: The purpose of this study was to use a near-infrared (NIR) fluorescent cyclic His-Try-Gly-Phe peptide to characterize and image the expressions of matrix metalloproteinases (MMPs), which are correlated with cancer promotion, in an inflammation-induced colorectal cancer (ICRC) model. We explored the relationship between the development of colon cancer and the expression of MMPs at the same colonic sites in ICRC models. To develop ICRC models, mice were administered a single intraperitoneal dose (10 mg/kg) of azoxymethane (AOM) and exposed orally to 2% dextran sodium sulfate (DSS) for one week. MMP-2 expression and β-catenin activation in colonic lesions were characterized by immunohistochemical (IHC) staining. After being treated with inducers for some time, cancerous lesions were found to express high β-catenin and MMP-2. The profiles of MMP expression were correlated with β-catenin activation in the colonic lesions. c(KAHWGFTLD)NH(2)  (C6) peptide was prepared by standard Fmoc peptide synthesis to target MMPs. Molecular weight of Cy5.5-C6 was 1,954.78 g/mol (calculated MW = 1955.23 g/mol). The in vitro characterization of Cy5.5-C6 showed MMP binding specificity in a cell experiment. In vivo NIRF imaging showed high accumulation of Cy5.5-C6 in tumors with associated expression of MMP-2 in colonic lesions after intravenous injection. The MMP-2 specificity of Cy5.5-C6 was confirmed by successful inhibition of probe uptake in the tumor due to the presence of excess C6 peptide. The use of Cy5.5-C6 to target MMP-2 has the potential to be developed into an effective molecular imaging agent to monitor ICRC progress.
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Chang-Moon
authors.initials: CM
authors.lastname: Lee
authors.forename: Doorye
authors.initials: D
authors.lastname: Jang
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Cheong
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Jeong
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D015153:Blotting, Western; D002232:Carbocyanines; D002273:Carcinogens / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate / Q000633:toxicity; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D018450:Disease Progression; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D002273:Carcinogens; D010446:Peptide Fragments; D051176:beta Catenin; D016264:Dextran Sulfate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001397:Azoxymethane