Reference : Stromal fibroblasts shape the myeloid phenotype in normal colon and colorectal cancer...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/51981

Title :	Stromal fibroblasts shape the myeloid phenotype in normal colon and colorectal cancer and induce CD163 and CCL2 expression in macrophages
Language :	English
Author, co-author :	Stadler, Mira [Institute of Medical Genetics, Medical University of Vienna, W¨ahringer Straße 10, A-1090 Vienna, Austria]
	Pudelko, Karoline [Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria]
	Biermeier, Alexander [Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria]
	Walterskirchen, Natalie [Department of Surgery, Medical University of Vienna, Währinger Gürtel 20, A-1090 Vienna, Austria]
	Gaigneaux, Anthoula [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Weindorfer, Claudia [Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria]
	Harrer, Nathalie [Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria, Dr. Boehringer-Gasse 5-11, A-1130 Vienna, Austri]
	Klett, Hagen [Charles River Research Services Germany GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany]
	Hengstschläger, Markus [Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria]
	Schüler, Julia [Charles River Research Services Germany GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany]
	Sommergruber, Wolfgang [Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria, Dr. Boehringer-Gasse 5-11, A-1130 Vienna, Austria]
	Oehler, Rudolf [Department of Surgery, Medical University of Vienna, Währinger Gürtel 20, A-1090 Vienna, Austria]
	Bergmann, Michael [Department of Surgery, Medical University of Vienna, Währinger Gürtel 20, A-1090 Vienna, Austria]
	Letellier, Elisabeth [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Dolznig, Helmut [Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria]
Publication date :	10-Jul-2021
Journal title :	Cancer Letters
Publisher :	Elsevier
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
ISSN :	0304-3835
e-ISSN :	1872-7980
City :	Limerick
Country :	Netherlands
Keywords :	[en] Cancer associated fibroblasts ; Colon cancer ; CCL2
Abstract :	[en] Colorectal cancer (CRC) accounts for about 10% of cancer deaths worldwide. Colon carcinogenesis is critically influenced by the tumor microenvironment. Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) represent the major components of the tumor microenvironment. TAMs promote tumor progression, angiogenesis and tissue remodeling. However, the impact of the molecular crosstalk of tumor cells (TCs) with CAFs and macrophages on monocyte recruitment and their phenotypic conversion is not known in detail so far. In a 3D human organotypic CRC model, we show that CAFs and normal colonic fibroblasts are critically involved in monocyte recruitment and for the establishment of a macrophage phenotype, characterized by high CD163 expression. This is in line with the steady recruitment and differentiation of monocytes to immunosuppressive macrophages in the normal colon. Cytokine profiling revealed that CAFs produce M-CSF, and IL6, IL8, HGF and CCL2 secretion was specifically induced by CAFs in co-cultures with macrophages. Moreover, macrophage/CAF/TCs co-cultures increased TC invasion. We demonstrate that CAFs and macrophages are the major producers of CCL2 and, upon co-culture, increase their CCL2 production twofold and 40-fold, respectively. CAFs and macrophages expressing high CCL2 were also found in vivo in CRC, strongly supporting our findings. CCL2, CCR2, CSF1R and CD163 expression in macrophages was dependent on active MCSFR signaling as shown by M-CSFR inhibition. These results indicate that colon fibroblasts and not TCs are the major cellular component, recruiting and dictating the fate of infiltrated monocytes towards a specific macrophage population, characterized by high CD163 expression and CCL2 production.
Funders :	Fonds National de la Recherche - FnR, the Fondation Marie-Jeanne and Edmond Schumacher, the Fondation Gustave and Simone Prévot.
Target :	Researchers
Permalink :	http://hdl.handle.net/10993/51981
DOI :	10.1016/j.canlet.2021.07.006
FnR project :	FnR ; FNR11282028 > Elisabeth Letellier > miRMet > Role Of Mir-371-373 Cluster In Tumor Initiation And Metastatic Colonization > 15/03/2017 > 14/07/2020 > 2016

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