Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
ISSN: 2157-7013
Lesley A. Mathews, Elaine M. Hurt, Xiaohu Zhang, William L. Farrar and Marc Ferrer
Scientific Tracks Abstracts: J Cell Sci Ther
Background: Recently, much attention has been focused on gaining a better understanding of the diff erent populations of cells within a tumor and their contribution to cancer progression. One of the most commonly used methods to isolate a more aggressive sub-population of cells utilizes cell sorting based on expression of certain cell adhesion molecules. A recently established method we developed is to isolate these more aggressive cells based on their properties of increased invasive ability. Th ese more invasive cells have been previously characterized as tumor initiating cells (TICs) that have a stem-like genomic signature and express a number of stem cell genes including Oct3/4 and Nanog and are more tumorigenic compared to their ?non-invasive? counterpart. Th ey also have a profi le reminiscent of cells undergoing a classic pattern of epithelial to mesenchymal transition or EMT. Using this model of invasion, we sought to investigate which genes are under epigenetic control in this rare population of cells. Epigenetic modifi cations, specifi cally DNA methylation, are key events regulating the process of normal human development. To determine the specifi c methylation pattern in these invasive prostate cells, and if any developmental genes were being diff erentially regulated, we analyzed diff erences in global CpG promoter methylation. Results: Diff erentially methylated genes were determined and select genes were chosen for additional analyses. Th e non-receptor tyrosine kinase BMX and transcription factor SOX1 were found to play a signifi cant role in invasion. Ingenuity pathway analysis revealed the methylated gene list frequently displayed genes from the IL-6/STAT3 pathway. Cells which have decreased levels of the targets BMX and SOX1 also display loss of STAT3 activity. Finally, using Oncomine, it was determined that more aggressive metastatic prostate cancers in humans also have higher levels of both Stat3 and Sox1 . Conclusions: Using this method we can begin to understand which genes are epigenetically regulated in the invasive population compared to the bulk tumor cells. Th ese aggressive sub- populations of cells may be linked to the cancer stem cell hypothesis, making their patterns of epigenetic regulation very attractive for biomarker analysis. Future Directions: Utilizing qHTS screening available at NCGC, new therapeutics aimed at eradicating highly aggressive tumor cells, either singularly or in combination, will be identifi ed