Cell‐fie of a Cancer Cell: Imaging Metastatic Potential of Single Living Tumor Cells with Fluorescent Biosensors

Abstract

Recognizing the metastatic potential of solid tumors is of utmost importance to personalize treatment plans for cancer patients. Conventional approaches utilize ensemble studies in which read‐outs from a heterogeneous population of cells are averaged to assess tumor aggressiveness. Such averaging obscures precious information on those individual tumor cells that are a minority within any given tumor, but possess the most ominous characteristics that contribute to their intrinsic metastatic potential, e.g., stem‐ness, EMT/invasiveness, drug resistance). Thus, the quest for the Holy Grail in measuring such ‘potential’ continues. Here we developed FRET‐based biosensors that measure the metastatic potential of single living cancer cells by confocal imaging.By design, these biosensors measure functional phosphorylation of Gα‐Interacting and Vesicle Associated Protein (GIV) a multimodular signal transducer and a bona‐fide metastasis‐related protein across a variety of solid tumors. These biosensors allow the generation of spatial and temporal signaling profiles of single cells, downstream of multiple receptors, even at a steady‐state. Such single‐cell signaling profiles are reflective of tumor heterogeneity, are unbiased to a given receptor/pathway, and eliminate the need to know which receptors/pathways drive a given tumor. Using these probes we detected those few cells within the primary lung and breast tumors with the highest metastatic potential, which are subsequently selected during metastasis.These results provide proof‐of‐concept that GIV‐biosensors are effective in monitoring the metastatic potential of single‐cells, in a sensitive and unbiased way, across different tumors.