Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment.
This work was supported by intramural funding from the Agency for Science, Technology and Research, Singapore (A*STAR) (core funding to W.L.T) Biomedical Research Council and the National Medical Research Council grant NMRC/TCR/016-NNI/2016, and Institute for Basic Science (IBS) IBS-R077-A1. Ex vivo images for this study were acquired at the SBICBruker Preclinical Imaging (PCI) Centre, Bruker Singapore (www.pci-lab.com).