GSE118624 Next Generation Sequencing of ovarian CA-MSC & MSC Transcriptomes

Contributors : Lan G Coffman ; Alex T Pearson ; Leonard G Frisbie ; Zackary Freeman ; Elizabeth L Christie ; David D Bowtell ; Ronald J BuckanovichSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCarcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer ‘stemness’ and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately d istinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of>0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, w...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research