Fluorescent imaging of in vivo H2O2 levels reveals contribution of oxidative microenvironment to tumor malignancy

Abstract

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) exert cytotoxic stress and perturbation of signal transduction on tumor cells to mediate redox imbalance that is a hallmark of cancer environment. However, establishing the role of ROS remains elusive in tumor progression, in part owing to a dearth of methods to study spatial dynamics of ROS in tumor microenvironment. Here, we have developed a peroxy green 1-conjugated anti-HER2 antibody that selectively visualize H2O2 to which HER2-positive tumor cells are exposed. This probe reveals highly heterogeneous H2O2 distribution in vivo in association with tumor development and neurophil accumulation in tumor-bearing models. Interestingly, functional and genetic analyses of tumor cells sorted on the basis of probe fluorescence demonstrate correlation of high H2O2 exposure with enhanced malignant phenotypes. Thus, our probe has potentiality to establish the importance of H2O2 microenvironment in promoting cancer malignancy.