Investigating the role of macrophages in tumor formation using a MaFIA mouse model

Clifford,A. B.; Elnaggar,A.  M.; Robison,R. A.; O'Neill,K.

doi:10.3892/or.2013.2508

August 2013 Volume 30 Issue 2

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August 2013 Volume 30 Issue 2

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Article

Investigating the role of macrophages in tumor formation using a MaFIA mouse model

Authors:
- A. B. Clifford
- A. M. Elnaggar
- R. A. Robison
- K. O'Neill
View Affiliations / Copyright

Affiliations: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA
Pages: 890-896
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Published online on: May 29, 2013

https://doi.org/10.3892/or.2013.2508
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Investigating the role of macrophages in tumor formation using a MaFIA mouse model

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