MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.

<h4>Background</h4>Myeloid-derived suppressor cells (MDSCs) function in immunosuppression and tumor development by induction of angiogenesis in a STAT3-dependent manner. Knowledge of MDSC biology is mainly limited to mice studies, and more clinical investigations using spontaneous tumor...

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Autores principales:	Joanna Mucha, Kinga Majchrzak, Bartłomiej Taciak, Eva Hellmén, Magdalena Król
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d429a3772ab8406dbdda2e92e13f78c0
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spelling	oai:doaj.org-article:d429a3772ab8406dbdda2e92e13f78c02021-11-25T06:06:44ZMDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.1932-620310.1371/journal.pone.0103249https://doaj.org/article/d429a3772ab8406dbdda2e92e13f78c02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25075523/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Myeloid-derived suppressor cells (MDSCs) function in immunosuppression and tumor development by induction of angiogenesis in a STAT3-dependent manner. Knowledge of MDSC biology is mainly limited to mice studies, and more clinical investigations using spontaneous tumor models are required. Here we performed in vitro experiments and clinical data analysis obtained from canine patients.<h4>Methods</h4>Using microarrays we examined changes in gene expression in canine mammary cancer cells due to their co-culture with MDSCs. Further, using Real-time rt-PCR, Western blot, IHC, siRNA, angiogenesis assay and migration/invasion tests we examined a role of the most important signaling pathway.<h4>Results</h4>In dogs with mammary cancer, the number of circulating MDSCs increases with tumor clinical stage. Microarray analysis revealed that MDSCs had significantly altered molecular pathways in tumor cells in vitro. Particularly important was the detected increased activation of IL-28/IL-28RA (IFN-λ) signaling. The highest expression of IL-28 was observed in stage III/IV mammary tumor-bearing dogs. IL-28 secreted by MDSCs stimulates STAT3 in tumor cells, which results in increased expression of angiogenic factors and subsequent induction of angiogenesis by endothelial cells, epithelial-mesenchymal transition (EMT) and increased migration of tumor cells in vitro. Knockdown of IL-28RA decreased angiogenesis, tumor cell invasion and migration.<h4>Conclusions</h4>We showed for the first time that MDSCs secrete IL-28 (IFN-λ), which promotes angiogenesis, EMT, invasion and migration of tumor cells. Thus, IL-28 may constitute an interesting target for further therapies. Moreover, the similarity in circulating MDSC levels at various tumor clinical stages between canine and human patients indicates canines as a good model for clinical trials of drugs targeting MDSCs.Joanna MuchaKinga MajchrzakBartłomiej TaciakEva HellménMagdalena KrólPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e103249 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joanna Mucha Kinga Majchrzak Bartłomiej Taciak Eva Hellmén Magdalena Król MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
description	<h4>Background</h4>Myeloid-derived suppressor cells (MDSCs) function in immunosuppression and tumor development by induction of angiogenesis in a STAT3-dependent manner. Knowledge of MDSC biology is mainly limited to mice studies, and more clinical investigations using spontaneous tumor models are required. Here we performed in vitro experiments and clinical data analysis obtained from canine patients.<h4>Methods</h4>Using microarrays we examined changes in gene expression in canine mammary cancer cells due to their co-culture with MDSCs. Further, using Real-time rt-PCR, Western blot, IHC, siRNA, angiogenesis assay and migration/invasion tests we examined a role of the most important signaling pathway.<h4>Results</h4>In dogs with mammary cancer, the number of circulating MDSCs increases with tumor clinical stage. Microarray analysis revealed that MDSCs had significantly altered molecular pathways in tumor cells in vitro. Particularly important was the detected increased activation of IL-28/IL-28RA (IFN-λ) signaling. The highest expression of IL-28 was observed in stage III/IV mammary tumor-bearing dogs. IL-28 secreted by MDSCs stimulates STAT3 in tumor cells, which results in increased expression of angiogenic factors and subsequent induction of angiogenesis by endothelial cells, epithelial-mesenchymal transition (EMT) and increased migration of tumor cells in vitro. Knockdown of IL-28RA decreased angiogenesis, tumor cell invasion and migration.<h4>Conclusions</h4>We showed for the first time that MDSCs secrete IL-28 (IFN-λ), which promotes angiogenesis, EMT, invasion and migration of tumor cells. Thus, IL-28 may constitute an interesting target for further therapies. Moreover, the similarity in circulating MDSC levels at various tumor clinical stages between canine and human patients indicates canines as a good model for clinical trials of drugs targeting MDSCs.
format	article
author	Joanna Mucha Kinga Majchrzak Bartłomiej Taciak Eva Hellmén Magdalena Król
author_facet	Joanna Mucha Kinga Majchrzak Bartłomiej Taciak Eva Hellmén Magdalena Król
author_sort	Joanna Mucha
title	MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
title_short	MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
title_full	MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
title_fullStr	MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
title_full_unstemmed	MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
title_sort	mdscs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via il-28/il-28ra (ifn-λ) signaling.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d429a3772ab8406dbdda2e92e13f78c0
work_keys_str_mv	AT joannamucha mdscsmediateangiogenesisandpredisposecaninemammarytumorcellsformetastasisviail28il28raifnlsignaling AT kingamajchrzak mdscsmediateangiogenesisandpredisposecaninemammarytumorcellsformetastasisviail28il28raifnlsignaling AT bartłomiejtaciak mdscsmediateangiogenesisandpredisposecaninemammarytumorcellsformetastasisviail28il28raifnlsignaling AT evahellmen mdscsmediateangiogenesisandpredisposecaninemammarytumorcellsformetastasisviail28il28raifnlsignaling AT magdalenakrol mdscsmediateangiogenesisandpredisposecaninemammarytumorcellsformetastasisviail28il28raifnlsignaling
_version_	1718414192531210240

MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.

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