(94d) Engineering Vasculogenesis to Determine the Vascular Anatomy Dependence of Circulating Tumor Cell Extravasation

Circulating tumor cells are known to preferentially metastasize to certain organ sites. A large number of studies have outlined the metastasis mechanism, however there still remain questions regarding tissue specific tropism. We hypothesize that vascular anatomy, ensuing hemodynamics, and near tissue microenvironment are critical to the attraction of metastasis cells. To address this, we have engineered implantable tissue microenvironments with tunable hydrogel scaffolds that reproducibly formed vascularized tissue analogues in vivo. Specifically we subdermally implanted 4 different hydrogel scaffolds with varying pore diameters (53-75, 150-180, 250-300 and 425-500 µm) in a single host mouse. After the scaffolds were implanted for 5 weeks, histological characterization revealed that scaffolds accommodated distinct vasculatures as a function of pore diameter. We next simulated circulating tumor cells by intravenously injecting 1-2 million cancer cells. Six hours later we retrieved the implanted scaffolds and determined the correlation between vasculature anatomy and systemic migration of cancer cells. Our results indicate that tissue dependent vascular anatomy is critical in recruiting specific types of circulating tumor cells. Engineered tissue microenvironments are expected to become a valuable platform for dissecting the metastasis mechanism and important parameters of the pro-metastatic niche.