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Nat Commun. 2013;4:2427. doi: 10.1038/ncomms3427.

Tumour angiogenesis regulation by the miR-200 family.

Author information

1
Department of Thoracic, Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
2
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
3
Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
4
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
5
Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
6
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
7
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
8
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
9
Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
10
Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
11
Department of Breast Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
12
Division of Allergy, Pulmonary and Critical Care Medicine, Thoracic Program, Vanderbilt Ingram Cancer Center and Veterans Affairs, Nashville, Tennessee 37232, USA.
#
Contributed equally

Abstract

The miR-200 family is well known to inhibit the epithelial-mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Using several experimental models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian, lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization. The role of miR-200 in blocking cancer angiogenesis in a cancer-dependent context defines its utility as a potential therapeutic agent.

PMID:
24018975
PMCID:
PMC3904438
DOI:
10.1038/ncomms3427
[Indexed for MEDLINE]
Free PMC Article

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