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

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.

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Publication Details

Journal
The Journal of Cell Biology
Published
2024-10-26
DOI
https://doi.org/10.1083/jcb.202403096
Citations
6
Primary Topic
Zebrafish Biomedical Research Applications
Type
article
Field-Weighted Citation Impact
1.96

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article

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

Miranda V. Hunter, Kevin W. Eliceiri, Veronika Miskolci, Richard M. White et al.
6 citations
The Journal of Cell Biology
Zebrafish Biomedical Research Applications
1.96
article

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

Miranda V. Hunter, Kevin W. Eliceiri, Veronika Miskolci, Richard M. White, Anna Huttenlocher A, Yiran Hou, Gayathri Ramakrishnan, Michael Lasarev, Daniela Münch, Morgan A. Giese
article en
6 citations

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.

The Journal of Cell BiologyVol. 224(2)
Stowers Institute for Medical Research (US), Memorial Sloan Kettering Cancer Center (US), University of Wisconsin–Madison (US), Morgridge Institute for Research (US), University of Oxford (GB), Ludwig Cancer Research (GB)
Arnold and Mabel Beckman Foundation, National Institutes of Health
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Openalex Percentile: Top 14%
Zebrafish Biomedical Research Applications
1.96
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