Expression of mouse CD47 on human cancer cells profoundly increases tumor metastasis in murine models

Abstract

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.