(190x) Implantable Humanized Pre-Metastatic Niches Capture Microenvironmental Regulation of Disseminated Human Tumor Cells

Metastatic relapse in secondary organs is the leading cause of cancer related death. Many cancer survivors carry disseminated tumor cells (DTCs) but do not experience relapse. Understanding how the local milieu regulates the transition from this quiescent state to active proliferation could lead to new therapeutic strategies to prevent or delay overt metastases. Here, we introduce a new approach to study in vivo metastasis by combining a tissue-inspired, implantable, humanized biomaterial microenvironment with human xenograft prostate cancer cells, stromal cells, and immune cells to capture and isolate dormant DTCs, and observe the phenotypic transition from dormancy to overt metastasis. Microfabricated porous hydrogel scaffolds formed and maintained key microenvironmental features of the pre-metastatic niche. Early stage metastases were separated from aggressively proliferating tumors by serial transplantation to naïve mice to prolong the experimental timeframe, thereby enabling the study of long-term dormancy of DTCs in vivo. A combination of whole tissue imaging and traditional histological analysis revealed the importance of vascular remodeling and continuous recruitment of innate immune cells during the transition from dormant to aggressive phenotypes. We envision that implantable pre-metastatic niches will be an enabling tool for studying the dormant microenvironment and aid in the development of effective anti-metastatic therapies.