Cancer-associated adipose tissue promotes breast cancer progression by paracrine oncostatin M and Jak/STAT3 signaling.

Autor:	Lapeire L; Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium., Hendrix A; Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium., Lambein K; Department of Pathology, Ghent University Hospital, Ghent, Belgium., Van Bockstal M; Department of Pathology, Ghent University Hospital, Ghent, Belgium., Braems G; Department of Gynaecology, Ghent University Hospital, Ghent, Belgium., Van Den Broecke R; Department of Gynaecology, Ghent University Hospital, Ghent, Belgium., Limame R; Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium., Mestdagh P; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium., Vandesompele J; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium., Vanhove C; Institute Biomedical Technology, Ghent University Hospital, Ghent, Belgium., Maynard D; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland., Lehuédé C; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, UPS, Toulouse, France., Muller C; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, UPS, Toulouse, France., Valet P; Institut National de la Santé et de la Recherche Médicale, INSERM U1048, Université Paul Sabatier, Toulouse, France., Gespach CP; Institut National de la Santé et de la Recherche Médicale, INSERM U938, Molecular and Clinical Oncology, Université Paris VI Pierre et Marie Curie, Paris, France., Bracke M; Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium., Cocquyt V; Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium., Denys H; Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium., De Wever O; Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium. olivier.dewever@ugent.be.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2014 Dec 01; Vol. 74 (23), pp. 6806-19. Date of Electronic Publication: 2014 Sep 24.
DOI:	10.1158/0008-5472.CAN-14-0160
Abstrakt:	Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer-associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells. A combination of techniques, including transcriptomics, proteomics, and kinomics enabled us to identify paracrine secretion of oncostatin M (OSM) by cancer-associated adipose tissue. Specifically, OSM, expressed by CD45(+) leucocytes in the stromal vascular fraction, induced phosphorylation of STAT3 (pSTAT3-) Y705 and S727 in breast cancer cells and transcription of several STAT3-dependent genes, including S100 family members S100A7, S100A8, and S100A9. Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSM-induced cellular scattering and peritumoral neovascularization of orthotopic xenografts. Conversely, selective inhibition of OSM by neutralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angiogenesis, and cellular scattering. Importantly, nuclear staining of pSTAT3-Y705 identified at the tumor invasion front in ductal breast carcinomas correlates with increased lymphovascular invasion. Our work reveals the potential of novel therapeutic strategies targeting the OSM and STAT3 axis in patients with breast cancer harboring nuclear pSTAT3-Y705. (©2014 American Association for Cancer Research.)
Databáze:	MEDLINE
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