Myeloid-Derived Suppressor Cells Enhance Stemness of Cancer Cells by Inducing MicroRNA101 and Suppressing the Corepressor CtBP2

• Published in: Immunity (Cambridge, Mass.) Mass.), 2013-09, Vol.39 (3), p.611-621
• Main Authors: Cui, Tracy X., Kryczek, Ilona, Zhao, Lili, Zhao, Ende, Kuick, Rork, Roh, Michael H., Vatan, Linda, Szeliga, Wojciech, Mao, Yujun, Thomas, Dafydd G., Kotarski, Jan, Tarkowski, Rafał, Wicha, Max, Cho, Kathleen, Giordano, Thomas, Liu, Rebecca, Zou, Weiping
• Format: Article
• Language: English
• Subjects: Alcohol Oxidoreductases - antagonists & inhibitors; Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - metabolism; Cell Communication; Female; Flow cytometry; Gene expression; Genotype & phenotype; Humans; Hypotheses; Immunology; Lymphocyte Activation; Lymphocytes; Medical prognosis; Medical research; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Myeloid Cells - cytology; Myeloid Cells - immunology; Myeloid Cells - metabolism; Neoplasm Metastasis; Neoplastic Stem Cells - immunology; Neoplastic Stem Cells - metabolism; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Ovarian cancer; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Patients; Plasmids; RNA Interference; RNA, Small Interfering; Studies; T-Lymphocytes - immunology; Tumors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.08.025

Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are important cellular components in the cancer microenvironment and may affect cancer phenotype and patient outcome. The nature of MDSCs and their interaction with CSCs in ovarian carcinoma are unclear. We examined the interaction between MDSCs and CSCs in patients with ovarian carcinoma and showed that MDSCs inhibited T cell activation and enhanced CSC gene expression, sphere formation, and cancer metastasis. MDSCs triggered miRNA101 expression in cancer cells. miRNA101 subsequently repressesed the corepressor gene C-terminal binding protein-2 (CtBP2), and CtBP2 directly targeted stem cell core genes resulting in increased cancer cell stemness and increasing metastatic and tumorigenic potential. Increased MDSC density and tumor microRNA101 expression predict poor survival, as does decreased tumor CtBP2 expression, independent of each other. Collectively, our work identifies an immune-associated cellular, molecular, and clinical network involving MDSCs-microRNA101-CtBP2-stem cell core genes, which extrinsically controls cancer stemness and impacts patient outcome. [Display omitted] •Myeloid-derived suppressor cells (MDSCs) stimulate microRNA101•MicroRNA101 targets CtBP2 and controls cancer stemness•As immune-suppressive components, MDSCs help reshape cancer phenotype•MDSC-microRNA101-CtBP2 network defines cancer invasiveness and outcome