Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy. JCI Insight 2016 Oct 20;1(17):e87754
Date
10/26/2016Pubmed ID
27777972Pubmed Central ID
PMC5070952DOI
10.1172/jci.insight.87754Scopus ID
2-s2.0-85055600619 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
Current antiangiogenesis therapy relies on inhibiting newly developed immature tumor blood vessels and starving tumor cells. This strategy has shown transient and modest efficacy. Here, we report a better approach to target cancer-associated endothelial cells (ECs), reverse permeability and leakiness of tumor blood vessels, and improve delivery of chemotherapeutic agents to the tumor. First, we identified deregulated microRNAs (miRs) from patient-derived cancer-associated ECs. Silencing these miRs led to decreased vascular permeability and increased maturation of blood vessels. Next, we screened a thioaptamer (TA) library to identify TAs selective for tumor-associated ECs. An annexin A2-targeted TA was identified and used for delivery of miR106b-5p and miR30c-5p inhibitors, resulting in vascular maturation and antitumor effects without inducing hypoxia. These findings could have implications for improving vascular-targeted therapy.
Author List
Mangala LS, Wang H, Jiang D, Wu SY, Somasunderam A, Volk DE, Lokesh GLR, Li X, Pradeep S, Yang X, Haemmerle M, Rodriguez-Aguayo C, Nagaraja AS, Rupaimoole R, Bayraktar E, Bayraktar R, Li L, Tanaka T, Hu W, Ivan C, Gharpure KM, McGuire MH, Thiviyanathan V, Zhang X, Maiti SN, Bulayeva N, Choi HJ, Dorniak PL, Cooper LJ, Rosenblatt KP, Lopez-Berestein G, Gorenstein DG, Sood AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic AgentsAptamers, Nucleotide
Cell Line, Tumor
Endothelial Cells
Humans
MicroRNAs
Nanoparticles
Neoplasms
Neovascularization, Pathologic
Transfection