title: Real-time subcellular imaging in live animals: new visible targets for cancer drug discovery.
abstract: 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.
authors.affiliation: AntiCancer Inc, 7917 Ostrow Street, San Diego, CA 92111-3604, USA. all@anticancer.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003952:Diagnostic Imaging; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D013347:Subcellular Fractions / Q000648:ultrastructure*
chemical_list: D000970:Antineoplastic Agents