Abstract
Abstract Intermedin (IMD) functions as an angiogenic factor in a rat ischemic model and human endothelial cells. In our search for anti-angiogenic therapy for solid tumors, we analyzed the expression and possible role of IMD in tumor angiogenesis. IMD was expressed in human colorectal adenocarcinoma (CRC) and hepatocellular carcinoma (HCC). The IMD expression was significantly higher in stage I than stage 0 of both colon and liver tumors (stage I/0 ratio of mRNA level is 7.7 ± 0.4 and 3.2 ± 0.3, respectively). IMD was widely expressed in colon and liver tumor lines. Immunohistochemistry showed that the tumor regions were significantly more immunoreactive for IMD than adjacent benign regions of CRC and HCC specimens. Inhibition of IMD expression by RNA interference reduced cell proliferation by 29.7 ± 6.7% (n = 3, p = 0.047) and impaired cell invasion by 27.8 ± 3.6% (n = 3, p = 0.016) in a HCC cell line SK-Hep-1. Addition of IMD peptide for 5 minutes to serum starved SK-Hep-1 cells increased the phosphorylation level of p44 and p42 MAP Kinase (Erk1/2), suggesting that IMD regulates Sk-Hep-1 cell growth, at least partly, through activating Erk1/2 signaling pathway. Similarly, IMD knockdown in a CRC cell line HCT116 reduced cell growth by 35.0 ± 1.4 % (n = 3, p = 0.018). Conditioned medium from IMD siRNA-transfected SK-Hep-1 cells reduced endothelial cell tube formation by 31.6 ± 6.8%. Conversely, over-expression of IMD in CRC RKO cells increased cell growth and induced cell migration significantly. Furthermore, treatment with RKO/IMD conditioned medium increased endothelial cell tube formation by 14. 7 ± 0.8% (n=4, p = 0.049). Thus, IMD stimulated HCC and CRC cell growth, migration, and invasion, indicating a role for IMD in tumor angiogenesis. 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 5149. doi:10.1158/1538-7445.AM2011-5149
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