(49c) Killing Metastatic Cancer Cells Using Immobilized TRAIL and E-Selectin: Combined Treatment with Chemotherapeutics
Most cancer related deaths are associated with the formation of secondary tumors as a result of metastasis. Circulating cancer cells interact with the endothelial lining of the vasculature via a series of adhesive interactions that facilitate tethering, firm adhesion and eventually transmigration to form secondary tumors. TNF-related apoptosis-inducing ligand (TRAIL) or APO2L holds promise as a tumor-specific cancer therapeutic, by inducing apoptosis via the extrinsic pathway. In this study we exploit the interaction of cancer cells with selectins and TRAIL to deliver a receptor-mediated apoptosis signal to captured cancer cells. We previously showed that a 1 hr rolling exposure to a functionalized TRAIL and E-selectin surface was sufficient to kill 30% of the captured cells compared to static conditions in which a 4 hr exposure was required to achieve a similar kill rate. When the same leukemic cells were pre-treated with 3ng/mL Bortezomib (Valcade®) and perfused over the TRAIL and selectin surface, a 40% kill rate was observed, while Bortezomib by itself killed only around 5% cells. In the case of colon cancer cells, pretreating with 1 mM Aspirin followed by rolling these cells over the combined surface, a 95% decrease in viability was seen between the cells that rolled over the combined TRAIL and E-selectin surface versus the E-selectin only surface. These synergistic results suggest a promising combined treatment scenario for the implantable device.