Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain

ELife
Kelda ChiaD Sieger

Abstract

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.

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Citations

Oct 17, 2019·Cold Spring Harbor Perspectives in Medicine·Katy R Astell, Dirk Sieger
Jan 8, 2020·Journal of Leukocyte Biology·Giuliano FerreroValérie Wittamer
Mar 13, 2020·Frontiers in Immunology·Frida SommerAnnemarie H Meijer
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Youngjin ParkViswanath Kiron
Jan 7, 2021·Cell Reports·Peiwen ChenRonald A DePinho
Oct 25, 2020·Cancers·Karolina A Zielińska, Vladimir L Katanaev
May 18, 2021·Frontiers in Cell and Developmental Biology·Paco López-CuevasPaul Martin
Jul 11, 2020·Cancer Cell·John D HayesKenneth D Tew
Sep 30, 2021·Molecular Medicine·Paola AllavenaCristina Belgiovine
Dec 17, 2021·Frontiers in Cell and Developmental Biology·Sarah A Neely, David A Lyons

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Methods Mentioned

BETA
transgenic
FACS
RNA assay
PCR

Software Mentioned

GraphPad
Prism
Imaris
LightCycler ® 96

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