Chem. Biol. doi:10.1016/j.chembiol.2014.03.012

Credit: ELSEVIER

Circulating tumor cells (CTCs) are responsible for metastasis that decreases survival for patients with cancer. The dissemination of these cells remains poorly understood owing to the inability to track the CTCs once they enter the circulation. Nedosekin et al. have developed a method that combines the ultrafast photoswitching of Dendra2 fluorescent protein with in vivo flow cytometry to enable labeling and tracking of a single CTC in the bloodstream. The authors focused their lasers on blood vessels where the blood flow allowed the CTC to pass through three laser beams, causing the cell to photoconvert from green to red. Once the cell changes its color, it can be tracked in vivo. In addition, the efficiency of photoconversion determined by the ratio of green to red fluorescence can be used as a unique fingerprint to follow individual CTCs that differ in their ratios. The authors wanted to use this system to determine pathways of recirculation and final destinations of CTCs when they exit from the primary tumor. They examined a mouse model of metastatic carcinoma in the ear, which released Dendra2-expressing CTCs. Upon photoconversion of these cells specifically in the tail vein, the authors found that some CTCs ended up residing not only in intact tissue and primary tumor, as established before, but also in existing metastases. This new technology will reveal more information about the behavior of CTCs, which may inspire new strategies for cancer therapeutics.