Published April 1, 2021 - More info
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.
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 corrigendum: JCI Insight. 2021;6(7):e149896. https://doi.org/10.1172/jci.insight.149896
The Editors previously posted an Expression of Concern for this article regarding images in Supplemental 4B that appeared similar (Endo40 and Endo42 samples) and images in Supplemental Figure 9 that appeared to be the same (CH and CH/Endo28-NPs for heart tissue). No changes were necessary for Supplemental Figure 4B, as the Endo40 and Endo42 samples were determined to be derived from adjacent tumor sections. An institutional review committee concluded that the error in Supplemental Figure 9 was inadvertent and recommended correction. The authors provided the correct image for the CH/Endo28-NPs sample from the original study. An updated supplemental file that includes the correct version of Supplemental Figure 9 is now posted.
The authors regret the error.
See the related article at Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy.