A team of researchers at the University of California San Diego School of Medicine (San Diego, CA) has developed biosensors that can detect and measure the metastatic potential of single cancer cells.
"Although there are many ways to detect metastasis once it has occurred, there has been nothing available to 'see' or 'measure' the potential of a tumor cell to metastasize in the future," says Pradipta Ghosh, MD, professor in the UC San Diego School of Medicine departments of Medicine and Cellular and Molecular Medicine, director of the Center for Network Medicine, and senior study author. "So at the Center for Network Medicine, we tackled this challenge by engineering biosensors designed to monitor not one, not two, but multiple signaling programs that drive tumor metastasis; upon sensing those signals, a fluorescent signal would be turned on only when tumor cells acquired high potential to metastasize, and therefore turn deadly."
Cancer cells alter normal cell communications by hijacking one of many signaling pathways to permit metastasis to occur. As the tumor cells adapt to the environment or cancer treatment, predicting which pathway will be used becomes difficult. By comparing proteins and protein modifications in normal vs. all cancer tissues, Ghosh and colleagues identified a particular protein and its unique modification called tyrosine-phosphorylated CCDC88A (GIV/Girdin) that are only present in solid tumor cells. Comparative analyses indicated that this modification could represent a point of convergence of multiple signaling pathways commonly hijacked by tumor cells during metastasis.
The team used novel engineered biosensors and sophisticated microscopes to monitor the modification on GIV and found that, indeed, fluorescent signals reflected a tumor cell's metastatic tendency. They were then able to measure the metastatic potential of single cancer cells and account for the unknowns of an evolving tumor biology through this activity. The result was the development of fluorescence resonance energy transfer (FRET) biosensors.
A tumor cell that has acquired high metastatic potential during chemotherapy lights up with high FRET biosensor readout, whereas the cells that are sensitive to chemotherapy (and hence, low potential) stays dark.
Although highly aggressive and adaptive, very few cancer cells metastasize and that metastatic potential comes and goes, Ghosh explains. If metastasis can be predicted, this data could be used to personalize treatment to individual patients. For example, patients whose cancer is not predicted to metastasize or whose disease could be excised surgically might be spared from highly toxic therapies, she says. Patients whose cancer is predicted to spread aggressively might be treated with precision medicine to target the metastatic cells.
"We have the potential not only to obtain information on single cell level, but also to see the plasticity of the process occurring in a single cell," Ghosh says. "This kind of imaging can be used when we are delivering treatment to see how individual cells are responding."
The sensors need further refinement, the study authors say, but have the potential to be a transformative advance for cancer cell biology.
Full details of the work appear in the journal iScience.