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  • 2020Journal Article
    [["dc.bibliographiccitation.firstpage","571"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Oncology"],["dc.bibliographiccitation.lastpage","589"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Arlt, Annekatrin"],["dc.contributor.author","Bonin, Frederike"],["dc.contributor.author","Rehberg, Thorsten"],["dc.contributor.author","Perez‐Rubio, Paula"],["dc.contributor.author","Engelmann, Julia C."],["dc.contributor.author","Limm, Katharina"],["dc.contributor.author","Reinke, Sarah"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Sun, Xueni"],["dc.contributor.author","Specht, Rieke"],["dc.contributor.author","Maulhardt, Markus"],["dc.contributor.author","Linke, Franziska"],["dc.contributor.author","Bunt, Gertrude"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dettmer, Katja"],["dc.contributor.author","Gronwald, Wolfram"],["dc.contributor.author","Oefner, Peter J."],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2021-04-14T08:27:44Z"],["dc.date.available","2021-04-14T08:27:44Z"],["dc.date.issued","2020"],["dc.description.abstract","Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination."],["dc.description.abstract","The study highlights the ability of Hodgkin lymphoma cells to attract and to differentiate monocytes into M2‐like Mφ and the role of IL13 in regulating CD206 but also that CD206 contributes to the remodeling of the tumor microenvironment via take up glycoconjugates as well as type‐I collagen and immunosuppression by PD‐L1 upregulation. image"],["dc.description.sponsorship","Stiftung der Georg‐August‐Universität"],["dc.description.sponsorship","Wilhelm‐Sander‐Stiftung"],["dc.description.sponsorship","Deutsche Krebshilfe http://dx.doi.org/10.13039/501100005972"],["dc.description.sponsorship","Bundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347"],["dc.description.sponsorship","Interreg"],["dc.identifier.doi","10.1002/1878-0261.12616"],["dc.identifier.eissn","1878-0261"],["dc.identifier.issn","1574-7891"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17183"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82387"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1878-0261"],["dc.relation.issn","1574-7891"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2017Journal Article Research Paper
    [["dc.bibliographiccitation.firstpage","361"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Leukemia"],["dc.bibliographiccitation.lastpage","372"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Linke, F."],["dc.contributor.author","Harenberg, M."],["dc.contributor.author","Nietert, M. M."],["dc.contributor.author","Zaunig, S."],["dc.contributor.author","Bonin, F. von"],["dc.contributor.author","Arlt, A."],["dc.contributor.author","Szczepanowski, M."],["dc.contributor.author","Weich, H. A."],["dc.contributor.author","Lutz, S."],["dc.contributor.author","Dullin, C."],["dc.contributor.author","Janovská, P."],["dc.contributor.author","Krafčíková, M."],["dc.contributor.author","Trantírek, L."],["dc.contributor.author","Ovesná, P."],["dc.contributor.author","Klapper, W."],["dc.contributor.author","Beißbarth, T."],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Bryja, V."],["dc.contributor.author","Trümper, L."],["dc.contributor.author","Wilting, J."],["dc.contributor.author","Kube, D."],["dc.date.accessioned","2018-11-07T10:28:03Z"],["dc.date.available","2018-11-07T10:28:03Z"],["dc.date.issued","2017"],["dc.description.abstract","The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) owing to its complex microenvironment. The role of the interplay between cHL and ECs remains poorly understood. Here we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and ECs. We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis toward ECs, adhesion to EC layers and cell invasion using not only the Wnt-inhibitor Dickkopf, tankyrases and casein kinase 1 inhibitors but also knockdown of the lymphocyte enhancer binding-factor 1 (LEF-1) and beta-catenin in cHL cells. Furthermore, LEF-1- and beta-catenin-regulated cHL secretome promoted EC migration, sprouting and vascular tube formation involving vascular endothelial growth factor A (VEGF-A). Importantly, high VEGFA expression is associated with a worse overall survival of cHL patients. These findings strongly support the concept that WNTs might function as a regulator of lymphoma dissemination by affecting cHL cell chemotaxis and promoting EC behavior and thus angiogenesis through paracrine interactions."],["dc.identifier.doi","10.1038/leu.2016.232"],["dc.identifier.isi","000394058800012"],["dc.identifier.pmid","27535218"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43339"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1476-5551"],["dc.relation.issn","0887-6924"],["dc.title","Microenvironmental interactions between endothelial and lymphoma cells: a role for the canonical WNT pathway in Hodgkin lymphoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]
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