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| Item Type: | Article |
|---|---|
| Title: | Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas |
| Creators Name: | Sielska, M. and Przanowski, P. and Pasierbińska, M. and Wojnicki, K. and Poleszak, K. and Wojtas, B. and Grzeganek, D. and Ellert-Miklaszewska, A. and Ku, M.C. and Kettenmann, H. and Kaminska, B. |
| Abstract: | 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. |
| Keywords: | Brain Neoplasms, Coculture Techniques, Disease Progression, Gene Knockdown Techniques, Genetic Databases, Glioma, Granulocyte-Macrophage Colony-Stimulating Factor, Jurkat Cells, Myeloid Cells, Neoplasm Invasiveness, Neoplasm Transplantation, Neoplastic Gene Expression Regulation, Tumor Cell Line, Up-Regulation, Animals, Mice |
| Source: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Volume: | 123 |
| Number: | 3 |
| Page Range: | 438-448 |
| Date: | 4 August 2020 |
| Official Publication: | https://doi.org/10.1038/s41416-020-0862-2 |
| PubMed: | View item in PubMed |
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