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Expression of mouse CD47 on human cancer cells profoundly increases tumor metastasis in murine models
Armando Rivera1, Xinping Fu2, Lihua Tao3
1Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas, USA. arivera8@central.uh.edu.
Background:
Many commonly used xenograft tumor models do not spontaneously metastasize to distant organs following subcutaneous or orthotopic implantation, limiting their usefulness in preclinical studies. It is generally believed that natural killer cells are the key component of the innate immune system in determining tumor metastatic potential in xenograft models. However, recent studies suggest that macrophages may play an important role, as resident macrophages can eliminate the invading tumor cells if they do not express adequate levels of the CD47 molecule.
Methods:
We investigated the effect of overexpressing murine CD47 (mCD47) in PC-3 cells, a commonly used human prostate cancer line, on the metastatic potential in three mouse strains with different genetic background and varying degrees of immunodeficiency. We implanted the tumor cells either subcutaneously or orthotopically and then examined their local and distant metastases.
Results:
Our results show that mCD47-expressing PC-3 cells subcutaneously implanted in NSG and CB17. Scid mice metastasized to the sentinel lymph node, lung and liver significantly more efficiently than the control cells. When implanted orthotopically to NOD. Scid mice, these cells spontaneously metastasized to lung and liver.
Conclusions:
Our data demonstrate that mCD47 can facilitate human tumor cell metastasis in murine models, and that these mCD47-expressing tumor cells may be useful for in vivo studies where spontaneous metastases are desirable.
Insights
Overexpressing CD47 in prostate cancer cells enhances their metastatic potential in mouse models. This finding is crucial for developing better preclinical models for studying cancer metastasis.
Area of Science:
- Oncology
- Immunology
- Cancer Metastasis Research
Background:
- Xenograft tumor models often lack spontaneous distant metastasis, limiting their preclinical utility.
- Natural killer cells are traditionally considered key in xenograft metastasis, but macrophages' role is emerging.
- Macrophages can eliminate tumor cells lacking sufficient CD47 expression.
Purpose of the Study:
- To investigate the impact of overexpressing murine CD47 (mCD47) on the metastatic potential of PC-3 human prostate cancer cells.
- To evaluate this effect across different mouse strains with varying immune deficiencies.
- To assess both local and distant metastatic capabilities following implantation.
Main Methods:
- PC-3 cells engineered to overexpress mCD47 were used.
- Tumor cells were implanted subcutaneously and orthotopically into three different mouse strains (NSG, CB17. Scid, NOD. Scid).
- Local and distant metastases were meticulously examined.
Main Results:
- Subcutaneous implantation of mCD47-expressing PC-3 cells led to significant metastasis to the sentinel lymph node, lung, and liver in NSG and CB17. Scid mice.
- Orthotopic implantation into NOD. Scid mice resulted in spontaneous metastasis to the lung and liver.
- Control cells showed significantly less metastatic activity.
Conclusions:
- Murine CD47 (mCD47) expression facilitates human tumor cell metastasis in mouse xenograft models.
- mCD47-expressing tumor cells represent a valuable tool for in vivo studies requiring spontaneous metastasis.
- This research enhances the utility of xenograft models for cancer metastasis research.
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