Dual-color-coded imaging of viable circulating prostate carcinoma cells reveals genetic exchange between tumor cells in vivo, contributing to highly metastatic phenotypes

被引:44
作者
Glinsky, GV
Glinskii, AB
Berezovskaya, O
Smith, BA
Jiang, P
Li, XM
Yang, M
Hoffman, RM
机构
[1] Ordway Res Inst Canc Ctr, Ctr Med Sci, New York, NY USA
[2] Sidney Ximmel Canc Ctr, San Diego, CA USA
[3] AntiCanc Inc, San Diego, CA USA
关键词
xenograft models; GFP; RFP; prostate cancer; orthotopic-implantation; nude mice; circulating cancer cells; lateral gene transfer;
D O I
10.4161/cc.5.2.2320
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Color-coded imaging analysis revealed yellow fluorescent metastasis precursor cells that were readily recognized in the blood of tumor-bearing mice after mixtures of red fluorescent protein (RFP)- and green fluorescent protein (GFP)-expressing PC-3 human prostate carcinoma cells were implanted in the nude mouse prostate and metastasized. The yellow fluorescent cells were purified from the blood of nude mice to 99% homogeneity by FACS, expanded in culture, and reimplanted in the prostate of nude mice. The yellow fluorescent phenotype was heritable and stably maintained by tumor cells for many generations in vitro and in vivo. In the animals implanted with the yellow-fluorescing cells, 100% developed aggressive metastatic cancer. Lung metastoses were demonstrated in 100% of the animals as early as four weeks after injection of the yellow-fluorescing cells in the mouse prostate. In contrast, when the GFP- and RFP-expressing parental cells were inoculated into the mouse prostate separately, none of the animals developed lung metastasis. All animals had almost exclusively yellow fluorescent cells in the blood and bone marrow. These results are consistent with the idea that spontaneous genetic exchange between tumor cells in vivo contributes to genomic instability and creation of highly metastatic cells.
引用
收藏
页码:191 / 197
页数:7
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