Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/121774
Title: EphA2-induced angiogenesis in ewing sarcoma cells works through bFGF production and is dependent on caveolin-1
Author: Sáinz Jaspeado, Miguel Guillermo
Huertas-Martínez, Juan
Lagares Tena, Laura
Martín Liberal, Juan Jesús
Mateo Lozano, Silvia
Alava, Enrique de
Torres Gómez-Pallete, Carmen de
Mora Graupera, Jaume
García del Muro Solans, Xavier
Tirado, Oscar M.
Keywords: Angiogènesi
Sarcoma d'Ewing
Endoteli
Neovascularization
Ewing's sarcoma
Endothelium
Issue Date: 12-Aug-2013
Publisher: Public Library of Science (PLoS)
Abstract: Angiogenesis is the result of the combined activity of the tumor microenvironment and signaling molecules. The angiogenic switch is represented as an imbalance between pro- and anti-angiogenic factors and is a rate-limiting step in the development of tumors. Eph receptor tyrosine kinases and their membrane-anchored ligands, known as ephrins, constitute the largest receptor tyrosine kinase (RTK) subfamily and are considered a major family of pro-angiogenic RTKs. Ewing sarcoma (EWS) is a highly aggressive bone and soft tissue tumor affecting children and young adults. As other solid tumors, EWS are reliant on a functional vascular network for the delivery of nutrients and oxygen and for the removal of waste. Based on the biological roles of EphA2 in promoting angiogenesis, we explored the functional role of this receptor and its relationship with caveolin-1 (CAV1) in EWS angiogenesis. We demonstrated that lack of CAV1 results in a significant reduction in micro vascular density (MVD) on 3 different in vivo models. In vitro, this phenomenon correlated with inactivation of EphA2 receptor, lack of AKT response and downregulation of bFGF. We also demonstrated that secreted bFGF from EWS cells acted as chemoattractant for endothelial cells. Furthermore, interaction between EphA2 and CAV1 was necessary for the right localization and signaling of the receptor to produce bFGF through AKT and promote migration of endothelial cells. Finally, introduction of a dominant-negative form of EphA2 into EWS cells mostly reproduced the effects occurred by CAV1 silencing, strongly suggesting that the axis EphA2-CAV1 participates in the promotion of endothelial cell migration toward the tumors favoring EWS angiogenesis.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0071449
It is part of: PLoS One, 2013, vol. 12, num. 8(8), p. e71449
URI: http://hdl.handle.net/2445/121774
Related resource: https://doi.org/10.1371/journal.pone.0071449
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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