Abstract 5300: Study heme oxygenase and imaging liver cancer in mice

Abstract

Abstract Liver cancer is the fifth most common cancer caused deaths worldwide and its incidence is increasing. The factors that influence the liver cancer progression are not clear. Recent reports show heme oxygenase-1 (HO-1) plays an important role in tumor progression and metastasis. Therefore, study the mechanism of HO-1 in liver cancer could potentially understand the liver cancer development and metastasis. We established two liver cancer cell lines that either contains wild- or mutant-type HO-1 gene to study the role of HO-1 in liver cancer metastasis. Matrigel invasion chambers assay was used to determine the invasion and migration of cells. The expression of IL-6, which is the key regulator of HO-1, was analyzed by real-time RT-PCR and ELISA for mRNA and protein, respectively. Two target-specific MMP and RGD peptides imaging agents were synthesized to follow up the liver cancer growth. Imaging studies were performed in cancer cells and xenograft models. In vivo imaging studies (n=10) were performed with peptide imaging agents and 18F fluoro-deoxy-glucose (18F-FDG) using optical, CT and PET scanning. The data demonstrated that overexpression of HO-1 significantly decreased the invasion ability of the liver cancer cells (P<0.05). Furthermore, the expression of IL-6 was also significantly decreased (P<0.05) in the wild-type HO-1 cells. The overexpression of mutant HO-1 significantly increased invasion ability (P<0.05) and the expression level of IL-6 (P<0.05). Cells treated by IL-6 siRNA down regulate the expression of IL-6 and decreased the invasion ability (P<0.05). The MMP peptide imaging agent, but not the free dye, bound to liver tumor cells in vitro and was internalized into the cells. Both cell and animal data confirmed that MMP imaging agent is taken up by liver cancer cells. RGD imaging agent was used to display blood vessel formation in the tumor regions. 18F-FDG PET imaging exhibited glucose metabolic stage in the disease site. It is found that the molecular imaging agents had different distributions in the body and differentially internalized into liver cancer cells. All target-specific agents yielded high tumor-to-background ratios after injection. In conclusion, HO-1 inhibited the invasion and migration of human hepatocellular cancer cell lines by regulating the expression of IL-6. Target-specific molecular imaging agents can be used to study liver cancer in vitro and in vivo. Noninvasive imaging with multi-target-specific molecular imaging agents could provide a tool for simultaneously studying multiple disease components. *CZ, WW: These authors contributed equally to this work. Grant support: DoD W81XWH-08-1-0489 (SK, WW), Department of Radiology research fund (SK, WW, MEM), National Science Foundation of China Grants 81000933 (CZ), Major State Basic Research Development Program of China 973 Program 2009CB521702 (XG). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5300. doi:10.1158/1538-7445.AM2011-5300