Colorectal cancer (CRC) is the second most recurrent cancer type and one of the most lethal diseases around the worldwide. The lethality of the CRC is due to the metastasis and the principal target is the liver. Although the main responsible of the metastasis is the cancer cell we can not obviate the crucial role of the host organ and how the cells of the host organ support the progression of the disease. The crosstalk of the tumor microenvironment with the tumor has been deeply studied from the cellular point of view but the regulatory pathways of these processes still remain unknown. The epigenetic regulation has been postulated as one important process implicated in the regulation of cellular changes. The microRNA (miRNA) expression is one of the variants of the epigenetic regulation. In this work we study the deregulation of the miRNA expression in the metastasized liver respect to healthy condition using a murine in vivo liver metastasis model.
We inoculated CT26 murine colon carcinoma cell intrasplenically in BALB/c mice and after 15 days we sacrificed the animals to obtain four liver cell types (hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells). Then we isolated the total RNA and performed gene expression and miRNA expression microarrays (Agilent) comparing the tumor received cells with control cells (PBS injected animal's cells). The gene expression microarray helps us finding the biological and cellular sense of the deregulated miRNAs and could be an important data source to elucidate the therapeutic option of each deregulated miRNAs. An in vivo approach is a more realistic model that can show more elements implicated in the crosstalk of the different liver cell types. This fact show us several results in the different cell types with expected and unexpected new miRNA deregulations. For instance downregulation of miR-16 and miR-15b and upregulation of miR-138 has been found in hepatic stellate cells with important role in activation proliferation and apoptosis of this cell type and we also observed deregulation of miR-135 in liver sinusoidal cells. These are some of the examples of a large amount of miRNA identified. Nowadays we are checking the role of each deregulated miRNA in the cellular processes to verify their implication in the metastatic progression and postulate them as therapeutic targets.
Citation Format: Joana Marquez, Arianne Schaub, Maite Unzurrunzaga, Patricia Garcia, Iker Badiola. MiRNA expression profile of tumor microenvironment in murine liver metastatic model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5347. doi:10.1158/1538-7445.AM2013-5347