[HTML][HTML] Tumour angiogenesis regulation by the miR-200 family

CV Pecot, R Rupaimoole, D Yang, R Akbani… - Nature …, 2013 - nature.com
CV Pecot, R Rupaimoole, D Yang, R Akbani, C Ivan, C Lu, S Wu, HD Han, MY Shah
Nature communications, 2013nature.com
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 …
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.
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