Tumour angiogenesis regulation by the miR-200 family

Chad V. Pecot, Rajesha Rupaimoole, Da Yang, Rehan Akbani, Cristina Ivan, Chunhua Lu, Sherry Wu, Hee-Dong Han, Maitri Y. Shah, Cristian Rodriguez-Aguayo, Justin Bottsford-Miller, Yuexin Liu, Sang Bae Kim, Anna Unruh, Vianey Gonzalez-Villasana, Li Huang, Behrouz Zand, Myrthala Moreno-Smith, Lingegowda S. Mangala, 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 Gonzalez-Angulo, Pierre P. Massion, George A. Calin, Gabriel Lopez-Berestein, Wei Zhang and Anil K. Sood ()
Additional contact information
Chad V. Pecot: Head and Neck Oncology, The University of Texas MD Anderson Cancer Center
Rajesha Rupaimoole: The University of Texas MD Anderson Cancer Center
Da Yang: The University of Texas MD Anderson Cancer Center
Rehan Akbani: The University of Texas MD Anderson Cancer Center
Cristina Ivan: The University of Texas MD Anderson Cancer Center
Chunhua Lu: The University of Texas MD Anderson Cancer Center
Sherry Wu: The University of Texas MD Anderson Cancer Center
Hee-Dong Han: The University of Texas MD Anderson Cancer Center
Maitri Y. Shah: The University of Texas MD Anderson Cancer Center
Cristian Rodriguez-Aguayo: The University of Texas MD Anderson Cancer Center
Justin Bottsford-Miller: The University of Texas MD Anderson Cancer Center
Yuexin Liu: The University of Texas MD Anderson Cancer Center
Sang Bae Kim: The University of Texas MD Anderson Cancer Center
Anna Unruh: The University of Texas MD Anderson Cancer Center
Vianey Gonzalez-Villasana: The University of Texas MD Anderson Cancer Center
Li Huang: The University of Texas MD Anderson Cancer Center
Behrouz Zand: The University of Texas MD Anderson Cancer Center
Myrthala Moreno-Smith: The University of Texas MD Anderson Cancer Center
Lingegowda S. Mangala: The University of Texas MD Anderson Cancer Center
Morgan Taylor: The University of Texas MD Anderson Cancer Center
Heather J. Dalton: The University of Texas MD Anderson Cancer Center
Vasudha Sehgal: The University of Texas MD Anderson Cancer Center
Yunfei Wen: The University of Texas MD Anderson Cancer Center
Yu Kang: The University of Texas MD Anderson Cancer Center
Keith A. Baggerly: The University of Texas MD Anderson Cancer Center
Ju-Seog Lee: The University of Texas MD Anderson Cancer Center
Prahlad T. Ram: The University of Texas MD Anderson Cancer Center
Murali K. Ravoori: The University of Texas MD Anderson Cancer Center
Vikas Kundra: The University of Texas MD Anderson Cancer Center
Xinna Zhang: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
Rouba Ali-Fehmi: Wayne State University School of Medicine, Karmanos Cancer Institute
Ana-Maria Gonzalez-Angulo: The University of Texas MD Anderson Cancer Center
Pierre P. Massion: Pulmonary and Critical Care Medicine, Thoracic Program, Vanderbilt Ingram Cancer Center and Veterans Affairs
George A. Calin: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
Gabriel Lopez-Berestein: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center
Wei Zhang: The University of Texas MD Anderson Cancer Center
Anil K. Sood: The University of Texas MD Anderson Cancer Center

Nature Communications, 2013, vol. 4, issue 1, 1-14

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3427

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