Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas
| Autor: | Katarzyna Poleszak, Bartosz Wojtas, Dominika Grzeganek, Maria Pasierbinska, Kamil Wojnicki, Aleksandra Ellert-Miklaszewska, Bozena Kaminska, Malgorzata Sielska, Piotr Przanowski, Min-Chi Ku, Helmut Kettenmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer microenvironment Cancer Research Myeloid Biology Article Jurkat Cells Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Glioma Databases Genetic medicine Animals Humans Macrophage Myeloid Cells Neoplasm Invasiveness 030304 developmental biology 0303 health sciences Gene knockdown Microglia Brain Neoplasms Mesenchymal stem cell Granulocyte-Macrophage Colony-Stimulating Factor medicine.disease Colony-stimulating factor Coculture Techniques Up-Regulation nervous system diseases Gene Expression Regulation Neoplastic Innate immune cells Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Oncology Gene Knockdown Techniques 030220 oncology & carcinogenesis Disease Progression Cancer research Function and Dysfunction of the Nervous System Neoplasm Transplantation medicine.drug |
| Zdroj: | British Journal of Cancer |
| Popis: | Background Malignant tumours release factors, which attract myeloid cells and induce their polarisation to pro-invasive, immunosuppressive phenotypes. Brain-resident microglia and peripheral macrophages accumulate in the tumour microenvironment of glioblastoma (GBM) and induce immunosuppression fostering tumour progression. Macrophage colony stimulating factors (CSFs) control the recruitment of myeloid cells during peripheral cancer progression, but it is disputable, which CSFs drive their accumulation in gliomas. Methods The expression of CSF2 (encoding granulocyte-macrophage colony stimulating factor) was determined in TCGA datasets and five human glioma cell lines. Effects of stable CSF2 knockdown in glioma cells or neutralising CSF2 or receptor CSF2Rα antibodies on glioma invasion were tested in vitro and in vivo. Results CSF2 knockdown or blockade of its signalling reduced microglia-dependent glioma invasion in microglia-glioma co-cultures. CSF2-deficient human glioma cells encapsulated in cell-impermeable hollow fibres and transplanted to mouse brains, failed to attract microglia, but stimulated astrocyte recruitment. CSF2-depleted gliomas were smaller, attracted less microglia and macrophages, and provided survival benefit in tumour-bearing mice. Apoptotic microglia/macrophages were detected in CSF2-depleted tumours. Conclusions CSF2 is overexpressed in a subset of mesenchymal GBMs in association with high immune gene expression. Tumour-derived CSF2 attracts, supports survival and induces pro-tumorigenic polarisation of microglia and macrophages. |
| Databáze: | OpenAIRE |
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