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
  • Cell Movement*
  • Mutation/genetics
  • Neoplasm Invasiveness*
  • Macrophages*/metabolism
  • Macrophages*/pathology
  • rac GTP-Binding Proteins/genetics
  • rac GTP-Binding Proteins/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Animals
  • Tumor Microenvironment
  • Humans
  • Melanoma*/genetics
  • Melanoma*/metabolism
  • Melanoma*/pathology
  • Zebrafish*
  • Cell Line, Tumor
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
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping