| Literature DB >> 24018975 |
Rajesha Rupaimoole1, Da Yang2, Rehan Akbani3, Chad V Pecot4, Cristina Ivan1,5, Chunhua Lu1, Sherry Wu1, Hee-Dong Han1, Maitri Y Shah6, Cristian Rodriguez-Aguayo6, Justin Bottsford-Miller1, Yuexin Liu2, Sang Bae Kim7, Anna Unruh3, Vianey Gonzalez-Villasana6, Li Huang8, Behrouz Zand1, Myrthala Moreno-Smith1, Lingegowda S Mangala1,5, Morgan Taylor1, Heather J Dalton1, Vasudha Sehgal7, Yunfei Wen1, Yu Kang1, Keith A Baggerly3, Ju-Seog Lee7, Prahlad T Ram7, Murali K Ravoori9, Vikas Kundra9, Xinna Zhang5,8, Rouba Ali-Fehmi10, Ana-Maria Gonzalez-Angulo7,11, Pierre P Massion12, George A Calin5,6, Gabriel Lopez-Berestein5,6,8, Wei Zhang2,5, Anil K Sood1,5,8.
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.Entities:
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Year: 2013 PMID： 24018975 PMCID： PMC3904438 DOI： 10.1038/ncomms3427
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919