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dc.contributor.authorCoffman, LG
dc.contributor.authorPearson, AT
dc.contributor.authorFrisbie, LG
dc.contributor.authorFreeman, Z
dc.contributor.authorChristie, E
dc.contributor.authorBowtell, DD
dc.contributor.authorBuckanovich, RJ
dc.date.accessioned2020-12-09T23:26:19Z
dc.date.available2020-12-09T23:26:19Z
dc.date.issued2019-02-01
dc.identifier.citationCoffman, L. G., Pearson, A. T., Frisbie, L. G., Freeman, Z., Christie, E., Bowtell, D. D. & Buckanovich, R. J. (2019). Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma. STEM CELLS, 37 (2), pp.257-269. https://doi.org/10.1002/stem.2932.
dc.identifier.issn1066-5099
dc.identifier.urihttp://hdl.handle.net/11343/253223
dc.description.abstractCarcinoma-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.
dc.languageEnglish
dc.publisherWILEY
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleOvarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma
dc.typeJournal Article
dc.identifier.doi10.1002/stem.2932
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleStem Cells
melbourne.source.volume37
melbourne.source.issue2
melbourne.source.pages257-269
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1353111
melbourne.contributor.authorChristie, Elizabeth
melbourne.contributor.authorBowtell, David
dc.identifier.eissn1549-4918
melbourne.accessrightsOpen Access


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