Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake
| Autor: | Niels Behrendt, Daniel H. Madsen, Majken S. Siersbæk, Loretta Grey Cloud, Lars Grøntved, Henrik J. Jürgensen, Shihui Liu, Dorota Ewa Kuczek, Thomas H. Bugge, Roberto Weigert |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Endocytic cycle Monocytes Collagen receptor endocytic matrix turnover Cell Movement Neoplasms extracellular matrix remodeling CCR2-derived TAMs lcsh:QH301-705.5 M2-polarized macrophages Monocytes/pathology Chemistry tumor-associated macrophages Cell Polarity Receptors CCR2/metabolism Transcriptome/genetics collagen endocytosis Neoplasms/genetics Endocytosis Cell biology Extracellular Matrix collagenases Collagenase Collagen cancer invasion Intravital microscopy Mannose Receptor medicine.drug Receptors CCR2 Receptors Cell Surface General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Macrophages/metabolism Collagen/metabolism medicine Extracellular Animals tumor microenvironment Lectins C-Type Cathepsin Inflammation Tumor microenvironment Macrophages Mesenchymal stem cell Extracellular Matrix/metabolism Rats Mice Inbred C57BL 030104 developmental biology Mannose-Binding Lectins lcsh:Biology (General) Proteolysis cathepsins Transcriptome Inflammation/pathology |
| Zdroj: | Cell Reports, Vol 21, Iss 13, Pp 3662-3671 (2017) Madsen, D H, Jürgensen, H J, Siersbæk, M S, Kuczek, D E, Grey Cloud, L, Liu, S, Behrendt, N, Grøntved, L, Weigert, R & Bugge, T H 2017, ' Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake ', Cell Reports, vol. 21, no. 13, pp. 3662-3671 . https://doi.org/10.1016/j.celrep.2017.12.011 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.12.011 |
| Popis: | Physiologic turnover of interstitial collagen is mediated by a sequential pathway in which collagen is fragmented by pericellular collagenases, endocytosed by collagen receptors, and routed to lysosomes for degradation by cathepsins. Here, we use intravital microscopy to investigate if malignant tumors, which are characterized by high rates of extracellular matrix turnover, utilize a similar collagen degradation pathway. Tumors of epithelial, mesenchymal, or neural crest origin all display vigorous endocytic collagen degradation. The cells engaged in this process are identified as tumor-associated macrophage (TAM)-like cells that degrade collagen in a mannose receptor-dependent manner. Accordingly, mannose-receptor-deficient mice display increased intratumoral collagen. Whole-transcriptome profiling uncovers a distinct extracellular matrix-catabolic signature of these collagen-degrading TAMs. Lineage-ablation studies reveal that collagen-degrading TAMs originate from circulating CCR2+ monocytes. This study identifies a function of TAMs in altering the tumor microenvironment through endocytic collagen turnover and establishes macrophages as centrally engaged in tumor-associated collagen degradation. Madsen et al. identify a population of tumor-associated macrophages with a distinct matrix catabolic signature as key effectors of collagen turnover during invasive tumor growth. These matrix-degrading macrophages are largely derived from CCR2+ monocytes reprogrammed by the tumor microenvironment and degrade collagen through mannose receptor-dependent cellular uptake. |
| Databáze: | OpenAIRE |
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