Aptamer Selection for Inhibition of Carcinoembryonic Antigen
The Main Idea
Carcinoembryonic Antigen (CEA) is a membrane glycoprotein that is overexpressed in individuals with colorectal carcinomas. Thus far, it has been shown that CEA is involved in signal transduction as well as cell-cell adhesion, and antibody-mediated therapies to inhibit CEA function are currently being developed. In a recent study, aptamer selection techniques were used to find an aptamer that bound to CEA at the "PELPK" sequence, thereby inhibiting the metastasis of colon cancer cells in mice. However, the isolated aptamer did not prevent cell adhesion among tumor cells. We hope to select for an aptamer that can both inhibit metastasis as well as cell adhesion by targeting a different amino acid sequence of CEA.
Specific Methods and Experiments
- A Review Article about CEA: This article broadly focuses on the research that has been done to characterize the structure and function of carcinoembryonic antigen family. It also talks about expression of CEA family members in normal cells as well as tumor cells. Overall, this paper will be helpful to us to find a.) more specific sources of information about CEA and b.) a general understanding of CEA functionality and how it can be targeted.
- Hammarstrom, S. (1999). The carcinoembryonic antigen ( CEA ) family : structures , suggested functions and expression in, 9.
- [Read this paper!]
- RNA Aptamer designed to inhibit CEA function: This article talks about how SELEX was used to identify an aptamer binding specifically to the "PELPK" sequence of the CEA glycoprotein. Although this aptamer seems to inhibit metastasis of colon cancer cells in mice, it does not affect cell-cell adhesion in tumors. We hope to use some of the methods from this paper to design an aptamer that will not only inhibit metastasis but also inhibit adhesion in tumor cells.
- Lee, Y. J., Han, S. R., Kim, N. Y., Lee, S.-H., Jeong, J.-S., & Lee, S.-W. (2012). An RNA Aptamer That Binds Carcinoembryonic Antigen Inhibits Hepatic Metastasis of Colon Cancer Cells in Mice. Gastroenterology. AGA Institute American Gastroenterological Association. doi:10.1053/j.gastro.2012.03.039
- [Read this paper!]
- Taheri, M., Saragovi, U., Fuks, a, Makkerh, J., Mort, J., & Stanners, C. P. (2000). Self recognition in the Ig superfamily. Identification of precise subdomains in carcinoembryonic antigen required for intercellular adhesion. The Journal of biological chemistry, 275(35), 26935-43. doi:10.1074/jbc.M909242199