Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy
Lingegowda S. Mangala, … , David G. Gorenstein, Anil K. Sood
Lingegowda S. Mangala, … , David G. Gorenstein, Anil K. Sood
Published October 20, 2016
Citation Information: JCI Insight. 2016;1(17):e87754. https://doi.org/10.1172/jci.insight.87754.
View: Text | PDF | Expression of Concern | Corrigendum
Research Article Angiogenesis Oncology

Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

  • Text
  • PDF
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

×

Figure 2

Selection and identification of thioaptamers that bind to human ovarian cancer vascular endothelial cells (ECs).

Options: View larger image (or click on image) Download as PowerPoint
Selection and identification of thioaptamers that bind to human ovarian ...
(A) Cell-SELEX procedure with thioaptamers (TAs). A library of ssDNA TAs was selected, and these TAs were incubated with purified human ovarian cancer ECs, washed, eluted, and amplified for 10 rounds. (B) Representative tumor sections showing binding of Endo28 to human ovarian tumor vasculature. Sections from normal ovary and tumor were incubated with Cy3-labeled Endo28 and anti-CD31 antibody to stain blood vessels. Nuclei are shown in blue, blood vessels in green, and Endo28 in red. Arrows denote colocalization of Endo28 (red) and CD31 (green). (C) Representative tumor sections showing expression of annexin A2 on human ovarian tumor vasculature. Sections from normal ovary and tumor were incubated with anti–annexin A2 and anti-CD31 antibodies. Nuclei are stained blue, annexin A2 green, and blood vessels red. Arrows denote colocalization of CD31 (red) and annexin A2 (green). (D) Annexin A2–positive human microvascular ECs (HMVECs) were detected by flow cytometry. (E) Representative immunofluorescence staining showing that silencing of annexin A2 resulted in reduced binding of Endo28 and Endo31 to HMVECs. Scale bars: 100 μm (C and E).

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts