Governing step of metastasis visualized in vitro
Governing step of metastasis visualized in vitro
复制标题
DOI：
10.1073/pnas.94.21.11573
复制
发表时间：
1997-10-14
影响因子：
11.1
通讯作者：
Hoffman, RM
中科院分区：
文献类型：
--
作者：
Chishima, T;Yang, M;Hoffman, RM
转移是癌症的最终危及生命的阶段。缺乏精确的模型系统阻碍了对转移细胞基础生物学的研究。为了连续跟踪转移性集落生长的后续阶段，我们通过转染GFP cDNA用绿色荧光蛋白（GFP）遗传标记来自人肺腺癌细胞系ANIP 973的细胞。然后将标记的细胞静脉内注射到裸鼠中，7天后，它们在小鼠肺上形成明亮的荧光转移集落[Chishima，T.，宫城，Y.，王，X.，杨，M.，谭，Y.，Shimada，H.，Moossa，A. R. &霍夫曼，R. M.（1997）Clin. Exp.转移15，547-552]。然后将接种的肺组织切除并在三维海绵凝胶基质支持的组织培养中孵育，该组织培养保持了体内肿瘤定植的关键特征，同时允许连续进入进行测量和操作。在52天的时间内，在相同的个体培养物中通过GFP荧光连续观察肿瘤进展，在此期间肿瘤扩散到整个肺。组织培养肿瘤定植对于肺癌细胞在肺组织上生长是选择性的，因为在组织培养的小鼠肝组织上没有生长，这也在体内观察到。支持组织培养中的选择性器官定殖和通过GFP荧光可视化肿瘤进展的能力允许转移的支配过程的体外研究[Kuo，T. H、久保田，T.，Watanbe，M.，Furukawa，T.，Teramoto，T.，Ishibiki，K.，Kitajima，M.，Moossa，A. R.，Penman，S. &霍夫曼，R. M.等人（1995）Proc. Acad. Sci. USA 92，12085-12089]。本文的结果为理解和开发预防和可能逆转转移的治疗方法提供了重要的新机会。
Metastasis is the ultimate life-threatening stage of cancer. The lack of accurate model systems thwarted studies of the metastatic cell's basic biology. To follow continuously the succeeding stages of metastatic colony growth, we heritably labeled cells from the human lung adenocarcinoma cell line ANIP 973 with green fluorescent protein (GFP) by transfection with GFP cDNA. Labeled cells were then injected intravenously into nude mice, where, by 7 days, they formed brilliantly fluorescing metastatic colonies on mouse lung [Chishima, T., Miyagi, Y., Wang, X., Yang, M., Tan, Y., Shimada, H., Moossa, A. R. & Hoffman, R. M. (1997) Clin. Exp. Metastasis 15, 547-552]. The seeded lung tissue was then excised and incubated in the three-dimensional sponge-gel-matrix-supported histoculture that maintained the critical features of progressive in vivo tumor colonization while al lowing continuous access for measurement and manipulation. Tumor progression was continuously visualized by GFP fluorescence in the same individual cultures over a 52-day period, during which the tumors spread throughout the lung. Histoculture tumor colonization was selective for lung cancer cells to grow on lung tissue, because no growth occurred on histocultured mouse liver tissue, which was also observed in vivo. The ability to support selective organ colonization in histoculture and visualize tumor progression by GFP fluorescence allows the in vitro study of the governing processes of metastasis [Kuo, T.-H., Kubota, T., Watanbe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M., Moossa, A. R., Penman, S. & Hoffman, R. M. (1995) Proc. Natl. Acad. Sci. USA 92, 12085-12089]. The results presented here provide significant, new opportunities to understand and to develop treatments that prevent and possibly reverse metastasis.