282535 Metabolomics and Integrated "Omics" Analysis of the Mesenchymal-Epithelial Transition in Ovarian Cancer

Tuesday, October 30, 2012: 9:36 AM
Crawford East (Westin )
Kathleen Vermeersch1, Lijuan Wang2, John McDonald2 and Mark P. Styczynski1, (1)School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, (2)School of Biology, Georgia Institute of Technology, Atlanta, GA

While there is a growing general awareness of the importance of metabolic changes in the onset and progression of cancer, the molecular basis and significance of these metabolic changes are only beginning to be understood. One aspect of cancer that is particularly poorly characterized - on the metabolic level as well as more generally - are transitions between epithelial and mesenchymal phenotypes. The epithelial-mesenchymal transition (EMT) is the process by which cells lose their epithelial characteristics and take on more mobile, mesenchymal-like phenotypes. MET is the reverse process, where cells convert from mesenchymal to epithelial phenotypes. Mesenchymal-like cancer cells are more migratory than epithelial-like cancer cells, more invasive, and more resistant to chemotherapy. EMT/MET are normal processes during organismal development, but they are hijacked by cancer cells, resulting in cells leaving the primary tumor site (EMT) and migrating to establish distant sites of tumor growth (MET). The mechanisms underlying these processes are also believed to play a role in conferring "cancer-initiating cell" (CIC) characteristics: stem cell-like properties including the potential to differentiate into the many cell types present in tumors. Thus, EMT/MET are the underlying processes necessary for metastatic cells to travel to and successfully colonize distant sites. While the molecular pathways of EMT/MET are still being uncovered, the metabolism of these processes has yet to be studied.

Recently, we created a novel ovarian cancer model of EMT/MET, processes that are difficult to observe or control in vivo or in vitro. Using HEY cells, which have a mesenchymal-like phenotype, we found that overexpression of the microRNA miR-429 results in MET1. This is the only existing in vitromiRNA-controlled model of ovarian cancer EMT/MET. In this work, we seek a multi-level "omics" characterization of MET. During miRNA-induced MET and susbsequent EMT reversion over the course of six days, samples are taken for metabolomics, proteomics, and transcriptomics analysis. Metabolomics analysis was done using two-dimensional gas chromatography coupled to mass spectrometry (GCxGC-MS) on mostly polar small molecule analytes.

We have found significant differences across multiple time points between MET and control samples based on both intracellular and extracellular metabolomics analyses. These results suggest that there is a distinct metabolic phenotype for epithelial and mesenchymal phenotypes; integration of proteomic and transcriptional data is being used to more fully understand these distinct phenotypes and to help identify whether there are metabolic aspects of MET and EMT that can be targeted for potential cancer treatments.

Reference:

1 Chen J, Wang L, Matyunina LV, Hill CG, McDonald JF. Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells. Gyn Oncol. 2011;121:200-5.


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See more of this Session: Proteomics & Metabolomic Approaches to Systems Biology
See more of this Group/Topical: Topical A: Systems Biology