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

Tumour angiogenesis regulation by the miR-200 family.

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  • 1Department of Thoracic, Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.

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
[PubMed - indexed for MEDLINE]
PMCID:
PMC3904438
Free PMC Article

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