Tumour angiogenesis regulation by the miR-200 family.

Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, Bottsford-Miller J, Liu Y, Kim SB, Unruh A, Gonzalez-Villasana V, Huang L, Zand B, Moreno-Smith M, Mangala LS, Taylor M, Dalton HJ, Sehgal V, Wen Y, Kang Y, Baggerly KA, Lee JS, Ram PT, Ravoori MK, Kundra V, Zhang X, Ali-Fehmi R, Gonzalez-Angulo AM, Massion PP, Calin GA, Lopez-Berestein G, Zhang W, Sood AK
Nat Commun. 2013 4: 2427

PMID: 24018975 · PMCID: PMC3904438 · DOI:10.1038/ncomms3427

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.

MeSH Terms (18)

Angiogenesis Inhibitors Breast Neoplasms Cell Movement Female Gene Expression Regulation, Neoplastic Gene Regulatory Networks Humans Interleukin-8 Lung Neoplasms MicroRNAs Models, Biological Nanoparticles Neoplasm Metastasis Neoplasms Neovascularization, Pathologic Oligonucleotides Pericytes Treatment Outcome

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