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PMID: 24012420 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2.

Immunity ·Vol. 39 ·No. 3 ·2013-09-19 ·Pages 611-21

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 W

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.

MeSH Terms
Alcohol Oxidoreductases/antagonists & inhibitors,genetics,metabolism Cell Communication Co-Repressor Proteins Female Humans Lymphocyte Activation MicroRNAs/genetics,metabolism Myeloid Cells/cytology,immunology,metabolism Neoplasm Metastasis Neoplastic Stem Cells/immunology,metabolism Nerve Tissue Proteins/antagonists & inhibitors,genetics,metabolism Ovarian Neoplasms/immunology,metabolism RNA Interference RNA, Small Interfering T-Lymphocytes/immunology
Chemicals
Co-Repressor Proteins MIRN101 microRNA, human MicroRNAs Nerve Tissue Proteins RNA, Small Interfering Alcohol Oxidoreductases CTBP2 protein, human
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Cui Tracy X
Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
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
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2013.08.025
Published
2013-09-19
Epub
2013-00-05
Pages
611-21
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3831370
Subset
IM
Grants
NCI NIH HHS · 5P30CA46592 · United States
NCI NIH HHS · CA099985 · United States
NCI NIH HHS · P30 CA046592 · United States
NCI NIH HHS · R01 CA171306 · United States
NCI NIH HHS · CA171306 · United States
NCI NIH HHS · R01 CA152470 · United States
NCI NIH HHS · R01 CA156685 · United States
NCI NIH HHS · CA123088 · United States
NCI NIH HHS · R01 CA123088 · United States
NCI NIH HHS · R01 CA099985 · United States
NCI NIH HHS · CA156685 · United States
NCI NIH HHS · R01 CA193136 · United States
Databases
GEO
GSE50082
External Links
PubMed source DOI: 10.1016/j.immuni.2013.08.025 PMC Full Text View journal details
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