title: Soluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.
abstract: Epithelial-mesenchymal transition (EMT) programmes provide cancer cells with invasive and survival capacities that might favour metastatic dissemination. Whilst signalling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumour cells and the tumour microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumour. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumours presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumours with little or no EMT. Taken together, our results show that EMT programmes trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favour cancer spread.
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.|Laboratory of Experimental Pathology (LEP), GIGA-Cancer, Liège, Belgium.
authors.forename: Meggy
authors.initials: M
authors.lastname: Suarez-Carmona
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Morgane
authors.initials: M
authors.lastname: Bourcy
authors.affiliation: INSERM UMR-S 903, Laboratoire Pol Bouin, University of Reims, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lesage
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Natacha
authors.initials: N
authors.lastname: Leroi
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Laïdya
authors.initials: L
authors.lastname: Syne
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.affiliation: Laboratory of Experimental Pathology (LEP), GIGA-Cancer, Liège, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
authors.affiliation: Laboratory of Experimental Pathology (LEP), GIGA-Cancer, Liège, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Erpicum
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: Laboratory of Experimental Pathology (LEP), GIGA-Cancer, Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.affiliation: INSERM UMR-S 903, Laboratoire Pol Bouin, University of Reims, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.affiliation: INSERM UMR-S 903, Laboratoire Pol Bouin, University of Reims, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
authors.affiliation: Laboratory of Tumour and Development Biology (LBTD), GIGA-Cancer, Liège, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Gilles
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D019899:Paracrine Communication; D010641:Phenotype; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D042501:Angiogenic Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines
keywords: angiogenesis; cancer; epithelial-mesenchymal transition; myeloid cells