UICC World Cancer Congress 2006

Methods: We have visualized cytoplasmic and nuclear dynamics during cancer-cell intravascular trafficking and extravasation in live mice with tumor cells labeled in the nucleus with GFP and with RFP in the cytoplasm. The mice were imaged with an Olympus OV100 whole-mouse imaging system with a sensitive CCD camera and five objective lenses, parcentered and parfocal, enabling imaging from macro to subcellular.

Results: We observed the nuclear and cytoplasmic behavior of cancer cells trafficking in blood vessels as they crawled along the vessel surface in an abdominal skin flap. The cancer cells deformed both nuclei and cytoplasm in order to move in small-diameter vessels. Some of the cancer cells were observed to form emboli from which cells could occasionally escape or other cells coalesce. Other cancer cells arrested by adhering to vessel walls from which some cells later were visualized to escape sometimes by contact with trafficking cancer cells. During extravasation, real-time imaging demonstrated that cytoplasmic processes of the cancer cells exited the vessels first, with nuclei following along the cytoplasmic projections. Both cytoplasm and nuclei underwent deformation during extravasation. Different cancer cell lines appeared to strongly vary in their ability to extravasate. The subcellular dynamics of cancer metastasis can now be visualized in live mice.