Arlt, Annekatrin and von Bonin, Frederike and Rehberg, Thorsten and Perez-Rubio, Paula and Engelmann, Julia C. and Limm, Katharina and Reinke, Sarah and Dullin, Christian and Sun, Xueni and Specht, Rieke and Maulhardt, Markus and Linke, Franziska and Bunt, Gertrude and Klapper, Wolfram and Vockerodt, Martina and Wilting, Joerg and Pukrop, Tobias and Dettmer, Katja and Gronwald, Wolfram and Oefner, Peter J. and Spang, Rainer and Kube, Dieter (2020) High CD206 levels in Hodgkin lymphoma-educated macrophages are linked to matrix-remodeling and lymphoma dissemination. MOLECULAR ONCOLOGY, 14 (3). pp. 571-589. ISSN 1574-7891, 1878-0261
Full text not available from this repository. (Request a copy)Abstract
Macrophages (M phi) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. M phi 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 M phi (TAM). Here, we show that the global mRNA expression and protein abundance of human M phi differentiated in Hodgkin lymphoma (HL)-conditioned medium (CM) differ from those of M phi 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 M phi; 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 M phi 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-ASSOCIATED MACROPHAGES; REED-STERNBERG CELLS; MANNOSE RECEPTOR; GENE-EXPRESSION; MICROENVIRONMENT; INTERLEUKIN-13; POLARIZATION; INHIBITOR; CYTOKINE; STRATEGY; CD206; lymphoma; macrophages; tumor microenvironment |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2021 08:13 |
| Last Modified: | 01 Apr 2021 08:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45312 |
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