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Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea

We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capaci...

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Published in:PloS one 2017-06, Vol.12 (6), p.e0179444-e0179444
Main Authors: Vilaseca, Antoni, Campillo, Noelia, Torres, Marta, Musquera, Mireia, Gozal, David, Montserrat, Josep M, Alcaraz, Antonio, Touijer, Karim A, Farré, Ramon, Almendros, Isaac
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Campillo, Noelia
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Farré, Ramon
Almendros, Isaac
description We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p
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An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p&lt;0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28594929</pmid><doi>10.1371/journal.pone.0179444</doi><tpages>e0179444</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2017-06, Vol.12 (6), p.e0179444-e0179444
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1907553407
source Publicly Available Content Database; PubMed Central
subjects Angiogenesis
Animal models
Animal models in research
Animals
Anoxia
Apnea
Biology and Life Sciences
Cancer
Carcinoma, Renal Cell - blood supply
Carcinoma, Renal Cell - complications
Carcinoma, Renal Cell - pathology
Care and treatment
Càncer de ronyó
Disease Models, Animal
Endothelial cells
Exposure
Gene expression
Genotype & phenotype
Hospitals
Hypoxia
Hypoxia - complications
Hypoxia - genetics
Hypoxia - pathology
Immune response
Immune system
In vitro methods and tests
Kidney
Kidney cancer
Kidney Neoplasms - blood supply
Kidney Neoplasms - complications
Kidney Neoplasms - genetics
Kidney Neoplasms - pathology
Macrophages
Macrophages - pathology
Male
Medicine and Health Sciences
Melanoma
Metastases
Metastasis
Mice, Inbred BALB C
Models animals en la investigació
Mortality
Neoplasm Metastasis
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - pathology
Obesity
Renal cancer
Renal cell carcinoma
Research and Analysis Methods
Rodents
Sleep
Sleep apnea
Sleep apnea syndromes
Sleep Apnea Syndromes - complications
Sleep Apnea Syndromes - genetics
Sleep Apnea Syndromes - pathology
Sleep disorders
Subcutaneous Tissue - pathology
Surgery
Síndromes d'apnea del son
Urology
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
Vascularization
title Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea
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