Rivera Armando, Fu Xinping, Tao Lihua, Zhang Xiaoliu
Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas, USA.
BMC Cancer. 2015 Dec 16;15:964. doi: 10.1186/s12885-015-1980-8.
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.
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.
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.
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.
许多常用的异种移植肿瘤模型在皮下或原位植入后不会自发转移至远处器官，这限制了它们在临床前研究中的用途。一般认为，自然杀伤细胞是先天免疫系统中决定异种移植模型中肿瘤转移潜能的关键组成部分。然而，最近的研究表明巨噬细胞可能起重要作用，因为驻留巨噬细胞可以清除那些不表达足够水平CD47分子的入侵肿瘤细胞。
我们研究了在常用的人前列腺癌PC-3细胞系中过表达小鼠CD47（mCD47）对三种具有不同遗传背景和不同程度免疫缺陷的小鼠品系转移潜能的影响。我们将肿瘤细胞皮下或原位植入，然后检查它们的局部和远处转移情况。
我们的结果表明，皮下植入NSG和CB17.Scid小鼠体内的表达mCD47的PC-3细胞转移至前哨淋巴结、肺和肝脏的效率明显高于对照细胞。当原位植入NOD.Scid小鼠体内时，这些细胞自发转移至肺和肝脏。
我们的数据表明，mCD47可促进人肿瘤细胞在小鼠模型中的转移，并且这些表达mCD47的肿瘤细胞可能对需要自发转移的体内研究有用。
