Optical Imaging of the MMP Expression and Cancer Progression in an Inflammation-Induced Colon Cancer Model : 염증성 대장암 모델에서 matrix metalloproteinases (MMP)의 발현과 암 성장의 광학 영상화 연구

다국어 초록 (Multilingual Abstract)

Purpose: Human colorectal cancer is one of the most common fatal malignancies. 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 a mouse model of inflammation-induced colorectal cancer (ICRC).
Materials and Methods: My first explored the relationship between the development of colon cancer and the expression of MMPs at the same colonic sites in ICRC models. MMP-2 expression and β-catenin activation in colonic lesions were characterized by immunohistochemical (IHC) staining. After verifying the expressions of the two proteins in induced cancer cells in the colon, c(KAHWGFTLD)NH2 (C6) peptide was prepared by standard Fmoc peptide synthesis to target MMPs. To develop a mouse model of ICRC, mice were administered a single intraperitoneal dose (10 mg/kg body weight) of azoxymethane (AOM) and exposed orally to 2% dextran sodium sulfate (DSS) for one week. In vivo MMP-targeted imaging of Cy5.5-C6 was performed using an IVIS optical imaging system in the ICRC model.
Results: The molecular weight of Cy5.5-C6 as determined by maldi-tof-ms analysis was 1954.78 (calculated MW = 1955.23). In the ICRC model, histological examination of colon cancer tissues was performed. After being treated with inducers for some time, cancerous lesions were found to express high β-catenin and MMP-2. The expressions of MMP profiles were correlated with MMP expression with β-catenin activation in the colonic lesions. The in vitro characterization of Cy5.5-C6 showed MMP binding specificity in a cell experiment. In vivo NIR fluorescence imaging showed high accumulation of Cy5.5-C6 in tumors with associated expression of MMP-2 in colonic lesions after intravenous injection.
Conclusion: The MMP-2 specificity of Cy5.5-C6 was confirmed by successful inhibition of probe uptake by the tumor in 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.

목차 (Table of Contents)

• Contents
• Abstract 1
• Introduction 4
• Materials and Methods 6
• Results and Discussion 12
• Conclusion 28
• References 29
• 국문초록 33