Organotypic Liver System for Tumor Progression

摘要

Our overall objective is to understand which tumor cell behaviors contribute to invasion and metastasis. This would allow rationale approaches to limit these aspects of tumor progression. While great strides have defined critical molecular determinants, the current experimental models of tumor invasion limit the dissection of complex cellular responses. In vitro assays do not capture tumor/host relations or relevant tissue architecture and physiology. In vivo model systems provide the relevant organism contexts but cannot readily be manipulated. Quantal advances would be enabled by combining the best attributes direct manipulation of tumor and host, long-term visualization, and tissue relevant architecture. Our central premise is that an ex vivo organotypic liver tissue system can provide an environment to study tumor cell invasion and metastasis. Our objective is to utilize a physiologically relevant microreactor that has proved suitable for organotypic liver culture to investigate metastatic seeding. The sub-millimeter scale of this liver allows for real-time imaging over weeks in culture. We established this system to determine what step is rate-limiting for tumor progression. We have now established an organotypic liver tissue culture that supports metastatic establishment and growth. This will be used to probe the molecular steps that are key to this progression.