IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancerReportar como inadecuado

IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Experimental and Clinical Cancer Research

, 32:97

First Online: 25 November 2013Received: 14 August 2013Accepted: 22 November 2013DOI: 10.1186-1756-9966-32-97

Cite this article as: Kachroo, P., Lee, MH., Zhang, L. et al. J Exp Clin Cancer Res 2013 32: 97. doi:10.1186-1756-9966-32-97


BackgroundInterleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial–mesenchymal transition EMT and angiogenesis are key processes in carcinogenesis. Although IL-27 has been shown to have potent anti-tumor activity in various cancer models, the role of IL-27 in EMT and angiogenesis is poorly understood. In this study, we investigated the role of IL-27 in regulating EMT and angiogenesis through modulation of the STAT pathways in human non-small cell lung carcinoma NSCLC cells.

MethodsSTAT activation following IL-27 exposure was measured in human NSCLC cell lines. Expression of epithelial E-cadherin, γ-catenin and mesenchymal N-cadherin, vimentin markers were assessed by Western blot analysis. Production of pro-angiogenic factors VEGF, IL-8-CXCL8, CXCL5 were examined by ELISA. Cell motility was examined by an in vitro scratch and transwell migration assays. Selective inhibitors of STAT1 STAT1 siRNAs and STAT3 Stattic were used to determine whether both STAT1 and STAT3 are required for IL-27 mediated inhibition of EMT and secretion of angiogenic factors.

ResultsOur results demonstrate that IL-27 stimulation in NSCLC resulted in 1 STAT1 and STAT3 activation in a JAK-dependent manner, 2 development of epithelial phenotypes, including a decrease in the expression of a transcriptional repressor for E-cadherin SNAIL, and mesenchymal marker vimentin with a reciprocal increase in the expression of epithelial markers, 3 inhibition of cell migration, and 4 reduced production of pro-angiogenic factors. STAT1 inhibition in IL-27–treated cells reversed the IL-27 effect with resultant increased expression of Snail, vimentin and the pro-angiogenic factors. The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype.

ConclusionIL-27 induces mesenchymal to epithelial transition and inhibits the production of pro-angiogenic factors in a STAT1–dominant pathway. These findings highlight the importance of STAT1 in repressing lung carcinogenesis and describe a new anti-tumor mechanism of IL-27.

KeywordsIL-27 STAT1 STAT3 Epithelial-mesenchymal transition Cytokine Angiogenesis Electronic supplementary materialThe online version of this article doi:10.1186-1756-9966-32-97 contains supplementary material, which is available to authorized users.

Puja Kachroo, Mi-Heon Lee contributed equally to this work.

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Autor: Puja Kachroo - Mi-Heon Lee - Ling Zhang - Felicita Baratelli - Gina Lee - Minu K Srivastava - Gerald Wang - Tonya C Wals


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