Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain
It is now clear that microglia and macrophages are present in brain tumors, but whether or how they affect initiation and development of tumors is not known. Exploiting the advantages of the zebrafish (Danio rerio) model, we showed that macrophages and microglia respond immediately upon oncogene act...
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doaj-255d8380a6f1430295963321963effef2021-05-05T15:36:51ZengeLife Sciences Publications LtdeLife2050-084X2018-02-01710.7554/eLife.31918Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brainKelda Chia0Julie Mazzolini1Marina Mione2https://orcid.org/0000-0002-9040-3705Dirk Sieger3https://orcid.org/0000-0001-6881-5183Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Integrative Biology (CIBIO), University of Trento, Trento, ItalyCentre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United KingdomIt is now clear that microglia and macrophages are present in brain tumors, but whether or how they affect initiation and development of tumors is not known. Exploiting the advantages of the zebrafish (Danio rerio) model, we showed that macrophages and microglia respond immediately upon oncogene activation in the brain. Overexpression of human AKT1 within neural cells of larval zebrafish led to a significant increase in the macrophage and microglia populations. By using a combination of transgenic and mutant zebrafish lines, we showed that this increase was caused by the infiltration of peripheral macrophages into the brain mediated via Sdf1b-Cxcr4b signaling. Intriguingly, confocal live imaging reveals highly dynamic interactions between macrophages/microglia and pre-neoplastic cells, which do not result in phagocytosis of pre-neoplastic cells. Finally, depletion of macrophages and microglia resulted in a significant reduction of oncogenic cell proliferation. Thus, macrophages and microglia show tumor promoting functions already during the earliest stages of the developing tumor microenvironment.https://elifesciences.org/articles/31918brain tumormacrophagesmicroglialive imagingtumor microenvironment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kelda Chia Julie Mazzolini Marina Mione Dirk Sieger |
spellingShingle |
Kelda Chia Julie Mazzolini Marina Mione Dirk Sieger Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain eLife brain tumor macrophages microglia live imaging tumor microenvironment |
author_facet |
Kelda Chia Julie Mazzolini Marina Mione Dirk Sieger |
author_sort |
Kelda Chia |
title |
Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain |
title_short |
Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain |
title_full |
Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain |
title_fullStr |
Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain |
title_full_unstemmed |
Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain |
title_sort |
tumor initiating cells induce cxcr4-mediated infiltration of pro-tumoral macrophages into the brain |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-02-01 |
description |
It is now clear that microglia and macrophages are present in brain tumors, but whether or how they affect initiation and development of tumors is not known. Exploiting the advantages of the zebrafish (Danio rerio) model, we showed that macrophages and microglia respond immediately upon oncogene activation in the brain. Overexpression of human AKT1 within neural cells of larval zebrafish led to a significant increase in the macrophage and microglia populations. By using a combination of transgenic and mutant zebrafish lines, we showed that this increase was caused by the infiltration of peripheral macrophages into the brain mediated via Sdf1b-Cxcr4b signaling. Intriguingly, confocal live imaging reveals highly dynamic interactions between macrophages/microglia and pre-neoplastic cells, which do not result in phagocytosis of pre-neoplastic cells. Finally, depletion of macrophages and microglia resulted in a significant reduction of oncogenic cell proliferation. Thus, macrophages and microglia show tumor promoting functions already during the earliest stages of the developing tumor microenvironment. |
topic |
brain tumor macrophages microglia live imaging tumor microenvironment |
url |
https://elifesciences.org/articles/31918 |
work_keys_str_mv |
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