title: Tumour angiogenesis regulation by the miR-200 family.
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.
authors.affiliation: Department of Thoracic, Head and Neck Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.initials: CV
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authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.lastname: Akbani
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Department of Breast Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.initials: AM
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authors.initials: PP
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authors.affiliation: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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authors.initials: GA
authors.lastname: Calin
authors.affiliation: Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 950, Houston, Texas 77030, USA.
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mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D053758:Nanoparticles / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics*; D009841:Oligonucleotides / Q000494:pharmacology / Q000627:therapeutic use; D020286:Pericytes / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D016209:Interleukin-8; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides
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