PUBLICATION

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

Authors
Chia, K., Mazzolini, J., Mione, M., Sieger, D.
ID
ZDB-PUB-180223-52
Date
2018
Source
eLIFE   7: (Journal)
Registered Authors
Mione, Marina, Sieger, Dirk
Keywords
brain tumor, cancer biology, immunology, inflammation, live imaging, macrophages, microglia, tumor microenvironment, zebrafish
MeSH Terms
  • Animals, Genetically Modified
  • Brain Neoplasms/pathology*
  • Signal Transduction
  • Humans
  • Proto-Oncogene Proteins c-akt/metabolism
  • Zebrafish Proteins/metabolism*
  • Cell Movement*
  • Macrophages/physiology*
  • Chemokine CXCL12/metabolism
  • Animals
  • Neuroglia/physiology
  • Disease Models, Animal
  • Zebrafish
  • Neoplastic Stem Cells/physiology*
  • Receptors, CXCR4/metabolism*
(all 15)
PubMed
29465400 Full text @ Elife
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.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ed7TgTransgenic Insertion
    gl22TgTransgenic Insertion
      gl23TgTransgenic Insertion
        hdb3TgTransgenic Insertion
          st95
            		Small Deletion
            t26035
              		Point Mutation
              1 - 6 of 6
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              No data available
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GFPEFGGFP
              mCherryEFGmCherry
              1 - 3 of 3
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              Mapping
              No data available
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              Citation
              Chia, K., Mazzolini, J., Mione, M., Sieger, D. (2018) Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral macrophages into the brain. eLIFE. 7.