Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial-to-mesenchymal transition (EMT) facilitates the invasion and metastasis of cancer cells. EMT seems to be mediated by the interaction between cancer cells and human mesenchymal stem cells (hMSCs) in the tumor microenvironment. The present study is intended to identify specific cytokines as potent inducers of EMT associated hMSCs-tumor interactions. We used ovarian cancer cell lines (SKOV-3 and IGROV-1), endometrial cancer cell line (Ishikawa) and hMSCs (bone marrow MSC, amniotic membrane MSC and decidua MSC). The expressions of EMT markers (E-cadherin, Snail, Twist and N-cadherin) were analyzed using quantitative RT-PCR, immunofluorescence and western blot analysis. Matrix metalloproteinases (MMP-2 and MMP-9), Matrigel invasion assay, and wound healing assay were used to analyze cell migration and invasion. Gynecologic cancer cells directly co-cultured with hMSCs had contact-dependent altered morphology and growth patterns. IL-6 was elevated in all co-cultures using a human cytokine array. After IL-6 treatment of cancer cell lines, RT-PCR and western blot analysis indicated a decrease in an epithelial marker and an increase in mesenchymal markers. Also, cancer cells with IL-6 significantly increase in MMP-2 and MMP-9 and significantly enhance the migration ability compared to untreated cells (P<0.05), as shown by wound healing assay. On Matrigel invasion assay, treated cells displayed significantly increased invasiveness compared to untreated cancer cells. Gyneocologic cancer cells exposed to IL-6 acquired mesenchymal properties that facilitated metastasis and invasion by promoting EMT. The present study suggests that IL-6 of the tumor microenvironment has a critical role in oncogenic EMT.
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PMID:Interleukin-6 expression by interactions between gynecologic cancer cells and human mesenchymal stem cells promotes epithelial-mesenchymal transition. 2631 17

Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA-MSCs differentially express bone morphogenetic protein family members, 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 global changes in CA-MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA-MSCs. Our classifier accurately distinguishes 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 from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. Although cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian TME can reprogram omental or ovary MSCs to protumorigenic CA-MSCs (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, although the breast cancer TME can reprogram bone marrow MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (a) provide a critical tool to define CA-MSCs and (b) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Stem Cells 2019;37:257-269.
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PMID:Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma. 3035 17