Abstract 3055: A permanent lung imaging window reveals, for the first time, the steps of extravasation, seeding and growth of early metastatic dissemination

Abstract

Abstract Metastatic disease is the major cause of cancer mortality and is responsible for over 1/2 million deaths each year in the U.S. alone. Of the three most common sites of metastasis observed clinically (bone, lung and liver), the most difficult to study using intravital microscopy is the lung; a delicate organ in perpetual motion. We have recently developed and validated an implantable, permanent, lung imaging window which allows high-resolution multiphoton imaging of the intact, breathing (without ventilation), murine lung over days to weeks of repeated imaging. This window does not use vacuum to immobilize the lung tissue thereby avoiding well know artifacts associated with vacuum lung windows. Using our new window, we have been able to visualize, with single cell resolution, the steps of metastasis in a clinically relevant, spontaneously-metastasizing murine breast cancer model. We present the first direct visualization of tumor cell arrival, extravasation, and progression to micro-metastases. Further, we have observed, for the first time, the activity of the tripartite structure called Tumor MicroEnvironment of Metastasis (TMEM) in metastatic lung lesions directly demonstrating the mechanism of dissemination from metastatic lung tumors. Using this approach to imaging live lung tissue serially, within a single animal, we are investigating the mechanisms underlying the fate of tumor cells arriving in the lung with the ultimate goal of directly identifying signals behind seeding and survival of metastatic tumor cells and their responses to interventions in real time. Citation Format: Sonia E. Voiculescu, Yarong Wang, Maja Oktay, John Condeelis, David Entenberg. A permanent lung imaging window reveals, for the first time, the steps of extravasation, seeding and growth of early metastatic dissemination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3055. doi:10.1158/1538-7445.AM2017-3055