Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy
Lingegowda S. Mangala, Hongyu Wang, Dahai Jiang, Sherry Y. Wu, Anoma Somasunderam, David E. Volk, Ganesh L. R. Lokesh, Xin Li, Sunila Pradeep, Xianbin Yang, Monika Haemmerle, Cristian Rodriguez-Aguayo, Archana S Nagaraja, Rajesha Rupaimoole, Emine Bayraktar, Recep Bayraktar, Li Li, Takemi Tanaka, Wei Hu, Cristina Ivan, Kshipra M Gharpure, Michael H. McGuire, Varatharasa Thiviyanathan, Xinna Zhang, Sourindra N. Maiti, Nataliya Bulayeva, Hyun-Jin Choi, Piotr L. Dorniak, Laurence J.N. Cooper, Kevin P. Rosenblatt, Gabriel Lopez-Berestein, David G. Gorenstein, and Anil K. Sood
Find articles by Mangala, L. in: JCI | PubMed | Google Scholar
Find articles by Wang, H. in: JCI | PubMed | Google Scholar
Find articles by Jiang, D. in: JCI | PubMed | Google Scholar
Find articles by Wu, S. in: JCI | PubMed | Google Scholar
Find articles by Somasunderam, A. in: JCI | PubMed | Google Scholar
Find articles by Volk, D. in: JCI | PubMed | Google Scholar
Find articles by Lokesh, G. in: JCI | PubMed | Google Scholar
Find articles by Li, X. in: JCI | PubMed | Google Scholar
Find articles by Pradeep, S. in: JCI | PubMed | Google Scholar
Find articles by Yang, X. in: JCI | PubMed | Google Scholar
Find articles by Haemmerle, M. in: JCI | PubMed | Google Scholar
Find articles by Rodriguez-Aguayo, C. in: JCI | PubMed | Google Scholar
Find articles by Nagaraja, A. in: JCI | PubMed | Google Scholar
Find articles by Rupaimoole, R. in: JCI | PubMed | Google Scholar
Find articles by Bayraktar, E. in: JCI | PubMed | Google Scholar
Find articles by Bayraktar, R. in: JCI | PubMed | Google Scholar
Find articles by Li, L. in: JCI | PubMed | Google Scholar
Find articles by Tanaka, T. in: JCI | PubMed | Google Scholar
Find articles by Hu, W. in: JCI | PubMed | Google Scholar
Find articles by Ivan, C. in: JCI | PubMed | Google Scholar
Find articles by Gharpure, K. in: JCI | PubMed | Google Scholar
Find articles by McGuire, M. in: JCI | PubMed | Google Scholar
Find articles by Thiviyanathan, V. in: JCI | PubMed | Google Scholar
Find articles by Zhang, X. in: JCI | PubMed | Google Scholar
Find articles by Maiti, S. in: JCI | PubMed | Google Scholar
Find articles by Bulayeva, N. in: JCI | PubMed | Google Scholar
Find articles by Choi, H. in: JCI | PubMed | Google Scholar
Find articles by Dorniak, P. in: JCI | PubMed | Google Scholar
Find articles by Cooper, L. in: JCI | PubMed | Google Scholar
Find articles by Rosenblatt, K. in: JCI | PubMed | Google Scholar
Find articles by Lopez-Berestein, G. in: JCI | PubMed | Google Scholar
Find articles by Gorenstein, D. in: JCI | PubMed | Google Scholar
Find articles by Sood, A. in: JCI | PubMed | Google Scholar
Published May 29, 2018 - More info
JCI Insight. 2018;3(11):e122387. https://doi.org/10.1172/jci.insight.122387.
Copyright © 2018, American Society for Clinical Investigation
Related article:
Abstract
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.
Authors
Lingegowda S. Mangala, Hongyu Wang, Dahai Jiang, Sherry Y. Wu, Anoma Somasunderam, David E. Volk, Ganesh L. R. Lokesh, Xin Li, Sunila Pradeep, Xianbin Yang, Monika Haemmerle, Cristian Rodriguez-Aguayo, Archana S Nagaraja, Rajesha Rupaimoole, Emine Bayraktar, Recep Bayraktar, Li Li, Takemi Tanaka, Wei Hu, Cristina Ivan, Kshipra M Gharpure, Michael H. McGuire, Varatharasa Thiviyanathan, Xinna Zhang, Sourindra N. Maiti, Nataliya Bulayeva, Hyun-Jin Choi, Piotr L. Dorniak, Laurence J.N. Cooper, Kevin P. Rosenblatt, Gabriel Lopez-Berestein, David G. Gorenstein, Anil K. Sood
Original citation: JCI Insight. 2016;1(17):e87754. https://doi.org/10.1172/jci.insight.87754
Citation for this expression of concern: JCI Insight. 2018;3(11):e122387. https://doi.org/10.1172/jci.insight.122387
The Editors recently became aware that the Endo40 and Endo42 samples in Supplemental Figure 4B appear to be similar. Additionally, in Supplemental Figure 9, the CH and CH/Endo28-NPs for the heart tissue appear to be the same. The Editorial Board is pursuing further investigation of this matter, and we will inform our readers of the outcome when the investigation is complete.
