Oncotarget

Research Papers:

In silico prediction of targets for anti-angiogenesis and their in vitro evaluation confirm the involvement of SOD3 in angiogenesis

Javier A. García-Vilas, Ian Morilla, Anibal Bueno, Beatriz Martínez-Poveda, Miguel Ángel Medina _ and Juan A.G. Ranea

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Oncotarget. 2018; 9:17349-17367. https://doi.org/10.18632/oncotarget.24693

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Abstract

Javier A. García-Vilas1, Ian Morilla1, Anibal Bueno1, Beatriz Martínez-Poveda1, Miguel Ángel Medina1,2 and Juan A.G. Ranea1,2

1Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, And IBIMA (Biomedical Research Institute of Málaga), Málaga, Spain

2CIBER de Enfermedades Raras (CIBERER), Málaga, Spain

Correspondence to:

Miguel Ángel Medina, email: [email protected]

Juan A.G. Ranea, email: [email protected]

Keywords: angiogenesis; matrigel assay; predictive networks; superoxide dismutase 3; wound scratch assay

Received: June 05, 2017    Accepted: February 24, 2018    Published: April 03, 2018

ABSTRACT

Biocomputational network approaches are being successfully applied to predict and extract previously unknown information of novel molecular components of biological systems. In the present work, we have used this approach to predict new potential targets of anti-angiogenic therapies. For experimental validation of predictions, we made use of two in vitro assays related to two key steps of the angiogenic process, namely, endothelial cell migration and formation of “tubular-like” structures on Matrigel. From 7 predicted candidates, experimental tests clearly show that superoxide dismutase 3 silencing or blocking with specific antibodies inhibit both key steps of angiogenesis. This experimental validation was further confirmed with additional in vitro assays showing that superoxide dismutase 3 blocking produces inhibitory effects on the capacity of endothelial cells to form “tubular-like” structure within type I collagen matrix, to adhere to elastin-coated plates and to invade a Matrigel layer. Furthermore, angiogenesis was also inhibited in the en vivo aortic ring assay and in the in vivo mouse Matrigel plug assay. Therefore, superoxide dismutase 3 is confirmed as a putative target for anti-angiogenic therapy.


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