Oncotarget

Research Papers:

The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization

Florian Finkernagel, Silke Reinartz, Sonja Lieber, Till Adhikary, Annika Wortmann, Nathalie Hoffmann, Tim Bieringer, Andrea Nist, Thorsten Stiewe, Julia M. Jansen, Uwe Wagner, Sabine Müller-Brüsselbach and Rolf Müller _

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Oncotarget. 2016; 7:75339-75352. https://doi.org/10.18632/oncotarget.12180

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Abstract

Florian Finkernagel1,*, Silke Reinartz2,*, Sonja Lieber1,*, Till Adhikary1, Annika Wortmann1, Nathalie Hoffmann1, Tim Bieringer1, Andrea Nist3, Thorsten Stiewe3, Julia M. Jansen2, Uwe Wagner2, Sabine Müller-Brüsselbach1, Rolf Müller1

1Institute of Molecular Biology and Tumor Research (IMT), Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany

2Clinic for Gynecology, Gynecological Oncology and Gynecological Endocrinology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany

3Genomics Core Facility, Center for Tumor Biology and Immunology (ZTI), Philipps University, Marburg, Germany

*These authors have contributed equally to this work

Correspondence to:

Rolf Müller, email: rmueller@imt.uni-marburg.de

Keywords: tumor-associated macrophages, resident peritoneal macrophages, macrophage polarization, transcriptional signature, extracellular matrix

Received: July 25, 2016     Accepted: September 09, 2016     Published: September 21, 2016

ABSTRACT

Macrophages occur as resident cells of fetal origin or as infiltrating blood monocyte-derived cells. Despite the critical role of tumor-associated macrophages (TAMs) in tumor progression, the contribution of these developmentally and functionally distinct macrophage subsets and their alteration by the tumor microenvironment are poorly understood. We have addressed this question by comparing TAMs from human ovarian carcinoma ascites, resident peritoneal macrophages (pMPHs) and monocyte-derived macrophages (MDMs). Our study revealed striking a similarity between TAMs and pMPHs, which was considerably greater that the resemblance of TAMs and MDMs, including their transcriptomes, their inflammation-related activation state, the presence of receptors mediating immune functions and the expression of tumor-promoting mediators. Consistent with these results, TAMs phagocytized bacteria, presented peptide antigens and activated cytotoxic T cells within their pathophysiological environment. These observations support the notion that tumor-promoting properties of TAMs may reflect, at least to some extent, normal features of resident macrophages rather than functions induced by the tumor microenvironment. In spite of these surprising similarities between TAMs and pMPHs, bioinformatic analyses identified a TAM-selective signature of 30 genes that are upregulated relative to both pMPHs and MDMs. The majority of these genes is linked to extracellular matrix (ECM) remodeling, supporting a role for TAMs in cancer cell invasion and ovarian cancer progression.


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