Abstract:
: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.
journal_name
Immunityjournal_title
Immunityauthors
Cui TX,Kryczek I,Zhao L,Zhao E,Kuick R,Roh MH,Vatan L,Szeliga W,Mao Y,Thomas DG,Kotarski J,Tarkowski R,Wicha M,Cho K,Giordano T,Liu R,Zou Wdoi
10.1016/j.immuni.2013.08.025subject
Has Abstractpub_date
2013-09-19 00:00:00pages
611-21issue
3eissn
1074-7613issn
1097-4180pii
S1074-7613(13)00377-4journal_volume
39pub_type
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