Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype

The vascular endothelial growth factor (VEGF) pathway is a clinically validated antiangiogenic target for non-small cell lung cancer (NSCLC). However, some contradictory results have been reported on the biological effects of antiangiogenic drugs. In order to evaluate the efficacy of these drugs in...

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Main Authors:	Larrayoz, Marta, Pio, Ruben, Pajares, María J, Zudaire, Isabel, Ajona, Daniel, Casanovas, Oriol, Montuenga, Luis M, Agorreta, Jackeline
Format:	Online
Language:	English
Published:	Backwell Publishing Ltd 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992079/

id	pubmed-3992079
recordtype	oai_dc
spelling	pubmed-39920792014-04-22 Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype Larrayoz, Marta Pio, Ruben Pajares, María J Zudaire, Isabel Ajona, Daniel Casanovas, Oriol Montuenga, Luis M Agorreta, Jackeline Research Articles The vascular endothelial growth factor (VEGF) pathway is a clinically validated antiangiogenic target for non-small cell lung cancer (NSCLC). However, some contradictory results have been reported on the biological effects of antiangiogenic drugs. In order to evaluate the efficacy of these drugs in NSCLC histological subtypes, we analyzed the anticancer effect of two anti-VEGFR2 therapies (sunitinib and DC101) in chemically induced mouse models and tumorgrafts of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Antiangiogenic treatments induced vascular trimming in both histological subtypes. In ADC tumors, vascular trimming was accompanied by tumor stabilization. In contrast, in SCC tumors, antiangiogenic therapy was associated with disease progression and induction of tumor proliferation. Moreover, in SCC, anti-VEGFR2 therapies increased the expression of stem cell markers such as aldehyde dehydrogenase 1A1, CD133, and CD15, independently of intratumoral hypoxia. In vitro studies with ADC cell lines revealed that antiangiogenic treatments reduced pAKT and pERK signaling and inhibited proliferation, while in SCC-derived cell lines the same treatments increased pAKT and pERK, and induced survival. In conclusion, this study evaluates for the first time the effect of antiangiogenic drugs in lung SCC murine models in vivo and sheds light on the contradictory results of antiangiogenic therapies in NSCLC. Backwell Publishing Ltd 2014-04 2014-02-05 /pmc/articles/PMC3992079/ /pubmed/24500694 http://dx.doi.org/10.1002/emmm.201303214 Text en © 2014 The Authors. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Larrayoz, Marta Pio, Ruben Pajares, María J Zudaire, Isabel Ajona, Daniel Casanovas, Oriol Montuenga, Luis M Agorreta, Jackeline
spellingShingle	Larrayoz, Marta Pio, Ruben Pajares, María J Zudaire, Isabel Ajona, Daniel Casanovas, Oriol Montuenga, Luis M Agorreta, Jackeline Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
author_facet	Larrayoz, Marta Pio, Ruben Pajares, María J Zudaire, Isabel Ajona, Daniel Casanovas, Oriol Montuenga, Luis M Agorreta, Jackeline
author_sort	Larrayoz, Marta
title	Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
title_short	Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
title_full	Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
title_fullStr	Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
title_full_unstemmed	Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
title_sort	contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype
description	The vascular endothelial growth factor (VEGF) pathway is a clinically validated antiangiogenic target for non-small cell lung cancer (NSCLC). However, some contradictory results have been reported on the biological effects of antiangiogenic drugs. In order to evaluate the efficacy of these drugs in NSCLC histological subtypes, we analyzed the anticancer effect of two anti-VEGFR2 therapies (sunitinib and DC101) in chemically induced mouse models and tumorgrafts of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Antiangiogenic treatments induced vascular trimming in both histological subtypes. In ADC tumors, vascular trimming was accompanied by tumor stabilization. In contrast, in SCC tumors, antiangiogenic therapy was associated with disease progression and induction of tumor proliferation. Moreover, in SCC, anti-VEGFR2 therapies increased the expression of stem cell markers such as aldehyde dehydrogenase 1A1, CD133, and CD15, independently of intratumoral hypoxia. In vitro studies with ADC cell lines revealed that antiangiogenic treatments reduced pAKT and pERK signaling and inhibited proliferation, while in SCC-derived cell lines the same treatments increased pAKT and pERK, and induced survival. In conclusion, this study evaluates for the first time the effect of antiangiogenic drugs in lung SCC murine models in vivo and sheds light on the contradictory results of antiangiogenic therapies in NSCLC.
publisher	Backwell Publishing Ltd
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992079/
_version_	1612079991840833536

Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype

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