Universität zu Köln

Doersam, Bastian, Boesl, Teresa, Reiners, Katrin S., Barnert, Sabine, Schubert, Rolf, Shatnyeva, Olga, Zigrino, Paola ORCID: 0000-0002-7470-0064, Engert, Andreas, Hansen, Hinrich P. and von Strandmann, Elke Pogge (2018). Hodgkin Lymphoma-Derived Extracellular Vesicles Change the Secretome of Fibroblasts Toward a CAF Phenotype. Front. Immunol., 9. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

Full text not available from this repository.

Abstract

Secretion of extracellular vesicles (EVs) is a ubiquitous mechanism of intercellular communication based on the exchange of effector molecules, such as growth factors, cytokines, and nucleic adds. Recent studies identified tumor-derived EVs as central players in tumor progression and the establishment of the tumor microenvironment (TME). However, studies on EVs from classical Hodgkin lymphoma (cHL) are limited. The growth of malignant Hodgkin and Rood Sternberg (HRS) cells depends on the TME, which is actively shaped by a complex interaction of HRS cells and stromal cells, such as fibroblasts and immune cells. HRS cells secrete cytokines and angiogenic factors thus recruiting and inducing the proliferation of surrounding cells to finally deploy an immunosuppressive TME. In this study, we aimed to investigate the role of tumor cell-derived EVs within this complex scenario. We observed that EVs collected from Hodgkin lymphoma (HL) cells were internalized by fibroblasts and triggered their migration capacity. EV-treated fibroblasts were characterized by an inflammatory phenotype and an upregulation of alpha-smooth muscle actin (alpha-SMA), a marker of cancer-associated fibroblasts. Analysis of the secretome of EV-treated fibroblast revealed an enhanced release of pro-inflammatory cytokines (e.g., IL-1 alpha, IL-6, and TNF-alpha), growth factors (G-CSF and GM-CSF), and pro-angiogenic factors such as VEGF. These soluble factors are known to promote HL progression. In line, ingenuity pathway analysis identified inflammatory pathways, including TNF-alpha/NF-kappa B signaling, as key factors directing the EV-dependent phenotype changes in fibroblasts. Confirming the in vitro data, we demonstrated that EVs promote alpha-SMA expression in fibroblasts and the expression of proangiogenic factors using a xenograft HL model. Collectively, we demonstrate that HL EVs alter the phenotype of fibroblasts to support tumor growth, and thus shed light on the role of EVs for the establishment of the tumor-promoting TME in HL.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Doersam, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Boesl, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiners, Katrin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barnert, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schubert, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Shatnyeva, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Zigrino, Paola UNSPECIFIED orcid.org/0000-0002-7470-0064 UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Hinrich P. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Strandmann, Elke Pogge UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-182786
DOI:	10.3389/fimmu.2018.01358
Journal or Publication Title:	Front. Immunol.
Volume:	9
Date:	2018
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LYMPHOCYTIC-LEUKEMIA CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER-ASSOCIATED FIBROBLASTS; PROMOTING TUMOR-GROWTH; STERNBERG CELLS; MICROENVIRONMENTAL INTERACTIONS; IMMUNE ESCAPE; EXOSOMES; EXPRESSION; STEMNESS Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18278