Open AccessContrasting responses of non‐small cell lung cancer to antiangiogenic therapies depend on histological subtype
Author(s) -
Larrayoz Marta,
Pio Ruben,
Pajares María J,
Zudaire Isabel,
Ajona Daniel,
Casanovas Oriol,
Montuenga Luis M,
Agorreta Jackeline
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303214
Subject(s) - cancer research , sunitinib , medicine , vascular endothelial growth factor , lung cancer , angiogenesis , in vivo , adenocarcinoma , cell growth , pathology , cancer , biology , vegf receptors , genetics , microbiology and biotechnology
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‐ VEGFR 2 therapies (sunitinib and DC 101) 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‐ VEGFR 2 therapies increased the expression of stem cell markers such as aldehyde dehydrogenase 1 A 1, CD 133, and CD 15, 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 .