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; Anil K. Sood

doi:10.1172/jci.insight.87754

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 IvanKshipra 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

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Article number	e87754
Journal	JCI Insight
Volume	1
Issue number	17
DOIs	https://doi.org/10.1172/jci.insight.87754
State	Published - Oct 20 2016

ASJC Scopus subject areas

General Medicine

Access to Document

10.1172/jci.insight.87754

Cite this

Mangala, L. S., Wang, H., Jiang, D., Wu, S. Y., Somasunderam, A., Volk, D. E., Lokesh, G. L. R., Li, X., Pradeep, S., Yang, X., Haemmerle, M., Rodriguez-Aguayo, C., Nagaraja, A. S., Rupaimoole, R., Bayraktar, E., Bayraktar, R., Li, L., Tanaka, T., Hu, W., ... Sood, A. K. (2016). Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy. JCI Insight, 1(17), Article e87754. https://doi.org/10.1172/jci.insight.87754

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, LJN, Rosenblatt, KP, Lopez-Berestein, G, Gorenstein, DG & Sood, AK 2016, 'Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy', JCI Insight, vol. 1, no. 17, e87754. https://doi.org/10.1172/jci.insight.87754

@article{900c40ccfb344f92ab3276a67584fcd6,

title = "Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy",

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.",

author = "Mangala, {Lingegowda S.} and Hongyu Wang and Dahai Jiang and Wu, {Sherry Y.} and Anoma Somasunderam and Volk, {David E.} and Lokesh, {Ganesh L.R.} and Xin Li and Sunila Pradeep and Xianbin Yang and Monika Haemmerle and Cristian Rodriguez-Aguayo and Nagaraja, {Archana S.} and Rajesha Rupaimoole and Emine Bayraktar and Recep Bayraktar and Li Li and Takemi Tanaka and Wei Hu and Cristina Ivan and Gharpure, {Kshipra M.} and McGuire, {Michael H.} and Varatharasa Thiviyanathan and Xinna Zhang and Maiti, {Sourindra N.} and Nataliya Bulayeva and Choi, {Hyun Jin} and Dorniak, {Piotr L.} and Cooper, {Laurence J.N.} and Rosenblatt, {Kevin P.} and Gabriel Lopez-Berestein and Gorenstein, {David G.} and Sood, {Anil K.}",

year = "2016",

month = oct,

day = "20",

doi = "10.1172/jci.insight.87754",

language = "English (US)",

volume = "1",

journal = "JCI Insight",

issn = "2379-3708",

publisher = "The American Society for Clinical Investigation",

number = "17",

}

TY - JOUR

T1 - Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

AU - Mangala, Lingegowda S.

AU - Wang, Hongyu

AU - Jiang, Dahai

AU - Wu, Sherry Y.

AU - Somasunderam, Anoma

AU - Volk, David E.

AU - Lokesh, Ganesh L.R.

AU - Li, Xin

AU - Pradeep, Sunila

AU - Yang, Xianbin

AU - Haemmerle, Monika

AU - Rodriguez-Aguayo, Cristian

AU - Nagaraja, Archana S.

AU - Rupaimoole, Rajesha

AU - Bayraktar, Emine

AU - Bayraktar, Recep

AU - Li, Li

AU - Tanaka, Takemi

AU - Hu, Wei

AU - Ivan, Cristina

AU - Gharpure, Kshipra M.

AU - McGuire, Michael H.

AU - Thiviyanathan, Varatharasa

AU - Zhang, Xinna

AU - Maiti, Sourindra N.

AU - Bulayeva, Nataliya

AU - Choi, Hyun Jin

AU - Dorniak, Piotr L.

AU - Cooper, Laurence J.N.

AU - Rosenblatt, Kevin P.

AU - Lopez-Berestein, Gabriel

AU - Gorenstein, David G.

AU - Sood, Anil K.

PY - 2016/10/20

Y1 - 2016/10/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85055600619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055600619&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.87754

DO - 10.1172/jci.insight.87754

M3 - Article

C2 - 27777972

AN - SCOPUS:85055600619

SN - 2379-3708

VL - 1

JO - JCI Insight

JF - JCI Insight

IS - 17

M1 - e87754

ER -

Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this