Discipline: Biological Sciences
Subcategory: Cancer Research
Jessica Ramirez Sanchez - California State University, Fullerton
Co-Author(s): Gen-Sheng Feng and Jin Lee, University of California, San Diego
Liver cancer is the second leading cause of cancer death worldwide. Liver tumors, specifically hepatocellular carcinoma, are linked to chronic inflammation in the immune system. The immune response in the liver tumor microenvironment involves inflammation that promotes or suppresses tumor formation depending on different immune factors. Poly I:C is a synthetic analog of double-stranded RNA, due to its structure and function with Toll-like receptor 3, and an immunostimulant which suppresses tumor formation in the liver. Shp2 is an enzyme that is involved in signaling events elicited by a variety of cytokines, and has been previously found to function as a tumor suppressor in liver cancer. When the Shp2 gene is deleted in the hepatocytes of mice, tumor promotion results in hepatocarcinoma. This study investigates whether Poly I:C has anti-tumor effects in diethylnitrosamine (DEN)-induced liver cancer in Shp2hep-/- mice by modulating anti-tumor immune responses. Poly I:C was hypothesized to provide immune regulation by balancing anti-tumor and pro-tumor responses in the liver. The anti-tumor effects were investigated by analyzing cell cycle regulatory proteins using Western blot, tumor macrophage development using immunohistochemistry, and measuring production of cytokines (CCL17, CCL22, Arg 1, IL-12) using qPCR. Results show that Poly I:C reduces tumor cell proliferation, and drastically decreases tumor macrophages and M2 pro-tumor cytokines. This study supports the role of Poly I:C as an immune regulator by balancing tumor responses in the liver. Future studies would require determining the mechanism of how Poly I:C reduces tumors in mice liver cancer. Ultimately, understanding the link between the immune system, specifically inflammation, and hepatocarcinogenesis will lead to a better understanding of liver cancer development which can evolve to cancer therapeutics for this deadly disease.
Funder Acknowledgement(s): UCSD STARS Program; CSUF Ronald E. McNair Scholars Program
Faculty Advisor: Gen-Sheng Feng,