Abstract P2-01-06: Intravital imaging of the lung reveals the efficiency of the metastatic cascade

Abstract

Abstract Background: Breast cancer is the leading cause of cancer related-death in women[1] with over 90% of these deaths due to metastasis. In these cases, the lung is the most common anatomical site of metastasis found at autopsy[2]. For the last 100 years, the process of metastasis has been studied through the use of an experimental metastasis (EM) assay [3] consisting of tail vein injection of tumor cells into tumor-free mice, followed by histopathological analysis of the lung weeks later to gain insight into tumor cell arrival, survival, and the growth of metastases. These studies have concluded that metastasis is an inefficient process[4]. Using a new technology developed at Albert Einstein College of Medicine, called the Window for High Resolution Imaging of the Lung (WHRIL)[5], we have directly compared EM to the more clinically relevant process of tumor cells spontaneously metastasizing (SM) from a primary tumor in situ to the lung and have found significant differences in metastatic efficiency between EM and SM. Methods: Real-time images of tumor cell dissemination were captured using the WHRIL (Figure 1) in both EM and SM models. Metastatic potential was analyzed, and compared between the models, the percentage of tumor cells surviving in the lung over time, their endothelial crossing-time, their frequency of interaction with macrophages, the fraction of cells which are dormant, and the percent of cells that developed into metastases. Results: Tumor cells which spontaneously metastasize from primary tumors show a ten-fold higher rate of survival in the lung and three times greater efficiency in forming metastases compared to those directly injected into the lung vasculature. Most of SM tumor cells are dormant indicating that the residual disease phenotype is programmed by the primary tumor either directly in the primary site or indirectly at the secondary site. Conclusion: These results indicate that experimental metastasis does not accurately reflect the true clinical process and that spontaneous dissemination from a primary tumor has significant influence on the survival and growth of disseminated cells. This suggests that the tumor microenvironment of the primary tumor educates disseminating tumor cells for survival, dormancy and growth at the primary site, and/or prepares the pre-metastatic niche, in the secondary site. Understanding where and how disseminated tumor cells are educated is critical to preventing their survival and growth.at secondary sites. This discovery will open the door to new strategies for the treatment of metastatic tumors to prevent metastatic progression and death. Citation Format: Coste AH, Boriello L, Wang Y, Oktay M, Condeelis JS, Entenberg D. Intravital imaging of the lung reveals the efficiency of the metastatic cascade [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-06.