Inhibition of tumor progression during allergic airway inflammation in a murine model: significant role of TGF-βReportar como inadecuado




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Cancer Immunology, Immunotherapy

, Volume 64, Issue 9, pp 1205–1214

First Online: 16 June 2015Received: 25 April 2014Accepted: 23 May 2015DOI: 10.1007-s00262-015-1722-4

Cite this article as: Tirado-Rodriguez, B., Baay-Guzman, G., Hernandez-Pando, R. et al. Cancer Immunol Immunother 2015 64: 1205. doi:10.1007-s00262-015-1722-4

Abstract

IntroductionTGF-β is an important mediator of pulmonary allergic inflammation, and it has been recently reported to be a potential inhibitor of lung tumor progression. The correlation between cancer and allergic inflammatory diseases remains controversial. Thus, the aim of the present study was to evaluate the effects of pulmonary allergic inflammation and in particular the role of TGF-β on cancer progression.

MethodsCancer cells were implanted in a BALB-c mice model of allergic airway inflammation, and tumor growth was measured. Apoptosis was evaluated by TUNEL assay, and TGF-β was measured by ELISA. Expression of proliferating cell nuclear antigen, TGF-β, TGF-β receptors I and II, phospho-Smad2 and phospho-Smad4 was evaluated by immunohistochemistry and quantified using digital pathology. The effect of a TGF-β activity inhibitor and recombinant TGF-β on tumor growth was analyzed. The effect of exogenous TGF-β on cell proliferation and apoptosis was evaluated in vitro.

ResultsMice with allergic airway inflammation exhibited decreased tumor volumes due to cell proliferation inhibition and increased apoptosis. TGF-β was increased in the sera and tumor tissues of allergic mice. TGF-β activity inhibition increased tumor progression in allergic mice by enhancing proliferation and decreasing apoptosis of tumor cells. The administration of TGF-β resulted in reduced tumor growth.

ConclusionThis study is the first to establish an inverse relationship between allergic airway inflammation and tumor progression. This effect appears to be mediated by TGF-β, which is overexpressed in tumor cells during pulmonary allergic inflammation. This study indicates that TGF-β is a potential target for antitumor therapy.

KeywordsAllergic airway inflammation Breast cancer TGF-β Apoptosis Allergo-oncology AbbreviationsAlumAluminum hydroxide

CTVCellTrace Violet

ELISAEnzyme-linked immunosorbent assay

HANHyperplastic alveolar nodule

i.p.Intraperitoneal

i.t.Intratracheal

I.T.Intratumoral

MAPKMitogen-activated protein kinase

OVAOvalbumin

PCNAProliferating cell nuclear antigen

HRPHorse-radish peroxidase

pSMAD-2Phosphorylated SMAD homologue 2

pSMAD-4Phosphorylated SMAD homologue 4

s.c.Subcutaneous

SMADIntracellular signal transduction proteins for transforming growth factor β receptors

SSSaline solution

TGF-βTransforming growth factor β

Th17Interleukin IL-17-producing T helper cells

Th1T helper type 1 cells

Th2T helper type 2 cells

TUNELTerminal deoxynucleotidyl transferase dUTP nick end labeling

TβRIITGF-β receptor II

TβRITGF-β receptor I

VEGFVascular endothelial growth factor

Laura C. Bonifaz and Sara Huerta-Yepez have contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00262-015-1722-4 contains supplementary material, which is available to authorized users.

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Autor: Belen Tirado-Rodriguez - Guillermina Baay-Guzman - Rogelio Hernandez-Pando - Gabriela Antonio-Andres - Mario I. Vega - Letic

Fuente: https://link.springer.com/







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