PUBLICATION

Real-time imaging reveals a role for macrophage protrusive motility in melanoma invasion

Authors
Ramakrishnan, G., Miskolci, V., Hunter, M., Giese, M.A., Münch, D., Hou, Y., Eliceiri, K.W., Lasarev, M.R., White, R.M., Huttenlocher, A.
ID
ZDB-PUB-241122-1
Date
2025
Source
The Journal of cell biology   224(2): (Journal)
Registered Authors
Huttenlocher, Anna, White, Richard M.
Keywords
none
MeSH Terms
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Cell Line, Tumor
  • Zebrafish*
  • Mutation/genetics
  • rac GTP-Binding Proteins/genetics
  • rac GTP-Binding Proteins/metabolism
  • Macrophages*/metabolism
  • Macrophages*/pathology
  • Tumor Microenvironment
  • Melanoma*/genetics
  • Melanoma*/metabolism
  • Melanoma*/pathology
  • Animals
  • Cell Movement*
  • Neoplasm Invasiveness*
  • Humans
(all 17)
PubMed
39570286 Full text @ J. Cell Biol.
Abstract
Macrophages are primary cells of the innate immune system that mediate tumor progression. However, the motile behavior of macrophages and interactions with tumor cells are not well understood. Here, we exploit the optical transparency of larval zebrafish and perform real-time imaging of macrophage-melanoma interactions. We found that macrophages are highly motile in the tumor microenvironment. Macrophages extend dynamic projections between tumor cells that precede invasive melanoma migration. Modulating macrophage motility with a dominant inhibitory mutation in Rac2 inhibits recruitment to the tumor and impairs tumor invasion. However, a hyperactivating mutation in Rac2 does not affect macrophage recruitment but limits macrophage projections into the melanoma mass and reduces invasive melanoma cell migration. Taken together, these findings reveal a role for Rac2-mediated macrophage protrusive motility in melanoma invasion.
Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
czt13TgTransgenic Insertion
    gl22TgTransgenic Insertion
      gl23TgTransgenic Insertion
        psi92TgTransgenic Insertion
          sh378TgTransgenic Insertion
            uwm27TgTransgenic Insertion
              uwm51TgTransgenic Insertion
                w2
                  Point Mutation
                  zdf1
                    Point Mutation
                    zf307TgTransgenic Insertion
                      1 - 10 of 11
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      BFPEFGBFP
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mCherryEFGmCherry
                      1 - 4 of 4
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                      Mapping
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