Tumour angiogenesis regulation by the miR-200 family

• DOI: 10.1038/ncomms3427
• Publication Date: 2013-09-10T10:00:30Z
• Authors: Chad V. Pecot; Rajesha Rupaimoole; Da Yang; Rehan Akbani; Cristina Ivan; Chunhua Lu; Sherry Wu; Hee-Dong Han; Maitri Y. Shah; Cristian Rodrigue...; Justin Bottsford-...; Yuexin Liu; Sang Bae Kim; Anna Unruh; Vianey Gonzalez-V...; Li Huang; Behrouz Zand; Myrthala Moreno-S...; Lingegowda S. Man...; Morgan Taylor; Heather J. Dalton; Vasudha Sehgal; Yunfei Wen; Yu Kang; Keith A. Baggerly; Ju-Seog Lee; Prahlad T. Ram; Murali K. Ravoori; Vikas Kundra; Xinna Zhang; Rouba Ali-Fehmi; Ana-Maria Gonzale...; Pierre P. Massion; George A. Calin; Gabriel Lopez-Ber...; Wei Zhang; Anil K. Sood
• Keywords: Lung Neoplasms; Oligonucleotides; General Physics and Astronomy; 610; Genetics and Molecular Biology; Angiogenesis Inhibitors; Breast Neoplasms; Models, Biological; 03 medical and health sciences; Cell Movement; Neoplasms; Humans; Gene Regulatory Networks; Neoplasm Metastasis; 0303 health sciences; Neovascularization, Pathologic; Interleukin-8; General Chemistry; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; Treatment Outcome; General Biochemistry; Nanoparticles; Female; Pericytes

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.