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Updated: May 11, 2026
A Macrophage-Tumor Spheroid Co-Invasion Assay
Published on: January 24, 2025
Investigating the role of macrophages in tumor formation using a MaFIA mouse model
A B Clifford1, A M Elnaggar, R A Robison
1Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Abstract:
Tumor-associated macrophages (TAMs) interact with tumors in their development, growth and metastatic activities. Using a transgenic mouse model that allows for the selective depletion of macrophages we were able to access the macrophage's potential to facilitate metastasis. In the MaFIA (Macrophage Fas-Induced Apoptosis) mouse, transgene-expressing cells of the myeloid lineage undergo death by apoptosis in the presence of the drug AP20187. Enhanced green fluorescent protein (EGFP) was fused to the suicide gene to allow identification of transgene-expressing cells. Tumor induction was accomplished by subdermal and intravenous injections of B16-F10 melanoma cells. Metastasis in mice with depleted macrophages was compared to metastasis in normal control mice. The lungs and kidneys were examined for metastatic cells. The macrophage-depleted groups showed significantly less metastasis (P>0.001) compared to the control groups. We theorize that macrophages may aid the metastatic process by fusing with melanoma cells. Using appropriate cell markers and fluorescence-activated cell sorting, we were able to detect a small population of double-positive cells. We confirmed cell fusion by microscopic analysis, visualizing the cell's morphology by both immunohistochemistry and immunofluorescence. The presence of double-positive cells suggests macrophage/cancer cell fusion could be a possible mechanism for metastasis.
Insights
Tumor-associated macrophages (TAMs) significantly contribute to cancer metastasis. Selective depletion of TAMs in mice reduced melanoma metastasis, suggesting TAMs facilitate tumor spread.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Tumor-associated macrophages (TAMs) play a crucial role in tumor progression, including metastasis.
- Understanding the specific mechanisms by which TAMs contribute to metastasis is vital for developing effective cancer therapies.
Purpose of the Study:
- To investigate the role of macrophages in facilitating cancer metastasis.
- To determine if selective depletion of macrophages impacts the metastatic potential of melanoma cells.
Main Methods:
- Utilized the MaFIA (Macrophage Fas-Induced Apoptosis) transgenic mouse model for selective macrophage depletion.
- Induced melanoma metastasis by injecting B16-F10 cells subdermally and intravenously.
- Quantified metastasis in lungs and kidneys of macrophage-depleted mice versus control mice.
- Investigated potential macrophage-cancer cell fusion using cell markers, fluorescence-activated cell sorting, immunohistochemistry, and immunofluorescence.
Main Results:
- Macrophage-depleted mice exhibited significantly reduced lung and kidney metastasis compared to control groups (P>0.001).
- Detected a population of double-positive cells, indicating fusion between macrophages and melanoma cells.
- Microscopic analysis confirmed the presence of fused macrophage-melanoma cells, supporting a fusion mechanism.
Conclusions:
- Macrophages significantly promote melanoma metastasis.
- Macrophage-cancer cell fusion is a potential mechanism contributing to tumor metastasis.
- Targeting TAMs or their fusion with cancer cells may represent a therapeutic strategy to inhibit metastasis.
