Hoffman Robert M
AntiCancer Inc, 7917 Ostrow Street, San Diego, CA 92111-3604, USA.
IDrugs. 2006 Sep;9(9):632-5.
This feature describes new in vivo imaging technology to visualize and identify novel targets for cancer drug discovery. AntiCancer Inc has developed dual-color fluorescent cells, with one color in the nucleus and another color in the cytoplasm, that enable visualization of real-time nuclear-cytoplasmic dynamics in living cells in vivo and in vitro, as well as nuclear dynamics and simultaneous cell and nuclear shape change. To obtain the dual-color cells, red fluorescent protein (RFP) was expressed in the cytoplasm of human and rodent cancer cells, and green fluorescent protein (GFP) that was linked to histone H2B was expressed in the nucleus. The migration velocities of the dual-color cancer cells in the capillaries were measured by capturing images of the fluorescent cells over time. The cells and nuclei in the capillaries were shown to elongate to fit the width of these vessels. Cancer cells in capillaries that were more than 8 mm in diameter were found to migrate. During extravasation, real-time imaging demonstrated that cytoplasmic processes of certain cancer cells exited the vessels first, with the nuclei then following along the cytoplasmic projections. Both the cytoplasm and nuclei underwent deformation during extravasation. Different cancer cell lines appear to vary strongly in their ability to extravasate. With the dual-color cancer cells and a highly sensitive whole-mouse imaging system (Olympus OV100), the subcellular dynamics of cancer metastasis can now be visualized in live mice. Further developments in subcellular imaging in live animals is expected to result in a new 'in vivo cell biology' that will provide visible targets for cancer and other diseases.
此特性描述了一种新型的体内成像技术，用于可视化和识别癌症药物研发的新靶点。抗癌公司已开发出双色荧光细胞，一种颜色在细胞核，另一种颜色在细胞质，能够在体内和体外活细胞中可视化实时核质动力学，以及核动力学和细胞与核形状的同时变化。为了获得双色细胞，红色荧光蛋白（RFP）在人和啮齿动物癌细胞的细胞质中表达，与组蛋白H2B相连的绿色荧光蛋白（GFP）在细胞核中表达。通过随时间捕获荧光细胞的图像来测量双色癌细胞在毛细血管中的迁移速度。毛细血管中的细胞和细胞核显示会伸长以适应这些血管的宽度。发现直径超过8毫米的毛细血管中的癌细胞会迁移。在渗出过程中，实时成像显示某些癌细胞的细胞质突起首先离开血管，随后细胞核沿着细胞质突起移动。在渗出过程中，细胞质和细胞核都会发生变形。不同的癌细胞系在渗出能力上似乎有很大差异。利用双色癌细胞和高灵敏度的全小鼠成像系统（奥林巴斯OV100），现在可以在活体小鼠中可视化癌症转移的亚细胞动力学。预计活体动物亚细胞成像的进一步发展将产生一种新的“体内细胞生物学”，为癌症和其他疾病提供可见靶点。
