Sonia E Voiculescu, MD, MPH1, David Entenberg, MsC2, Yarong Wang, MD2, Maja Oktay, MD, PhD1, John Condeelis, PhD2. 1Montefiore Medical Center, 2Albert Einstein College of Medicine
OBJECTIVE OF TECHNOLOGY: There are over 1.7 million worldwide cases of breast cancer diagnosed yearly, making it the most common female malignancy, with 90% of deaths caused by metastasis. The past decade of research has made it clear that the microenvironment dominates tumor phenotype, resulting in dissemination, and intravital microscopy has been at the forefront of discovery. At the primary site, we have used high-resolution, single-cell, intravital imaging to identify the Tumor Microenvironment of Metastasis (TMEM), a tripartite structure composed of a tumor cell, macrophage, and endothelial cell in direct contact with one another and functioning as the sole doorway through which tumor cells disseminate hematogenously. One of the most common destinations of metastasis, is the lung, a delicate organ in perpetual motion incapable of long-term imaging up until recently. We have developed and validated the first implantable, permanent window for high-resolution imaging of the lung (WHRIL), which produces stable, high-resolution imaging for up to two weeks.
METHODS: A minimally-invasive technique was developed to permanently implant a 9mm stainless-steel imaging window, secured in place using purse-string sutures and cyanoacrylate, creating a “transparent ribcage” in the mouse. Microcartography, a mathematical algorithm was used re-localize positions of interest, allowing us to study the same microenvironment down to an individual tumor cell for weeks.
RESULTS: We visualized the progression of tumor cells from first arrival to formation of micro-metastases. Mice show no signs of local or systemic inflammation and easily withstand repeated imaging. This has enabled us to visualize the exact steps of metastasis and has allowed us to observe TMEM at all sites and all stages, establishing a common mechanism for re-dissemination of tumor cells even once the primary tumor has been removed.
CONCLUSIONS: Through the partnership of surgery, engineering, and bench-side research, we have made intravital imaging less invasive, dramatically extending the time that a single mouse may be imaged. We now have observed the arrival, extravasation, and progression to micro-metastases of the same tumor cells over days to weeks. We are beginning to discover that TMEM, the mechanism facilitating hematogenous dissemination of tumor cells is common to most adeno carcinomas, not limited to breast cancer models. This technique allows us to further investigate the fate of metastasizing tumor cells including the factors of dormancy, proliferation, re-dissemination, and response to treatment.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 90991
Program Number: ET006
Presentation Session: Emerging Technology Session (Non CME)
Presentation Type: Podium