NewTumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells abstract created on Monday June 29, 2015

Abstract

Event Abstract Back to Event NewTumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells abstract created on Monday June 29, 2015 Elly De Vlieghere1, Marc Bracke1, Pieter Demetter2, Wim Ceelen3, Christain Vanhove4, Bruno G. De Geest5 and Olivier De Wever1 1 Ghent University, Laboratory of Experimental Cancer Research, Belgium 2 Erasme University Hospital, Department of Pathology, Belgium 3 Ghent University Hospital, Department of Surgery, Belgium 4 Ghent University, INFINITY, Belgium 5 Ghent University, Laboratory of Pharmaceutical Technology, Belgium Introduction: Biomimetics of the tumor-environment, an ecosystem, can be applied to create an ecological trap. An ecological trap is an environment of low quality for survival that is preferred by an organism over a better available environment. Carcinoma associated cancer cells (CAFs) produce an extracellular matrix (ECM) that exerts a high attraction to disseminated cancer cells, and is the perfect bait for an ecological trap. Microparticle encapsulated CAFs (MP[CAF]) can redirect adhesion of disseminated cancer cells from the peritoneal wall to the MP[CAF] surface to prevent peritoneal metastasis formation. Materials and Methods: Encapsulation: CAFs cells are encapsulated into microparticles (MP[CAF] 500-700µm) by dripping a mixture of alginate (1.5%), gelatin (0.5%) and CAFs (2.106/ml) in to a CaCl2 bath (1.3%) though a needle (260µm inner diameter) surrounded by an airflow. MP[CAF] where layer-by-layer coated with poly-styrene sulfonate and poly-allyamine (PSS/PAH), with or without the incorporation of iron-oxide nanoparticles between the layers. In vitro confrontation assay: MP[CAF] and MPs without CAFs where confronted with luciferase positive cancer cells (1.105) while shaking. After 48h adhesion the two types of MPs are magnetically separated and the adhesion of SK-OV-3 Luc on the MPs is measured through bioluminescence. In vivo: MP[CAF] (200) are inserted through a small incision in to the abdominal cavity of nude mice. 1.105 ovarian cancer cells (SK-OV-3 Luc IP1) are injected. 24h later MPs with captured cancer cells are removed with a magnet. Sham threated mice underwent the same procedure but now MPs where inserted. Results and Discussion: MP[CAF] are stable and encapsulated CAFs are viable and metabolic active for over 4 weeks. CAF-derived ECM proteins are retained by the PSS/PAH coating. In vitro confrontation show that cancer cells have a higher affinity for MP[CAF] compared to empty MP (fig 1A-B). Small animal MRI imaging shows distribution of MP throughout the abdominal cavity without attachment to intestinal organs and without signs of inflammatory reaction. MP[CAF] trap cancer cells and redirect adhesion away from the wound site. Removal of the MP[CAF] results in a delay peritoneal metastasis formation and a prolonged survival in mice (fig 2A-D). Conclusion: Biomimetics of the tumor-environment by encapsulating CAFs creates an ecological trap for disseminated cancer cells. The present results demonstrate the potential of ecological traps to prevent cancer metastasis. Vlaamse Liga tegen Kanker; Stichting tegen Kanker; IWT