title: TRAIL-coated leukocytes that kill cancer cells in the circulation.
abstract: Metastasis through the bloodstream contributes to poor prognosis in many types of cancer. Mounting evidence implicates selectin-based adhesive interactions between cancer cells and the blood vessel wall as facilitating this process, in a manner similar to leukocyte trafficking during inflammation. Here, we describe a unique approach to target and kill colon and prostate cancer cells in the blood that causes circulating leukocytes to present the cancer-specific TNF-related apoptosis inducing ligand (TRAIL) on their surface along with E-selectin adhesion receptor. This approach, demonstrated in vitro with human blood and also in mice, mimics the cytotoxic activity of natural killer cells and increases the surface area available for delivery of the receptor-mediated signal. The resulting "unnatural killer cells" hold promise as an effective means to neutralize circulating tumor cells that enter blood with the potential to form new metastases.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mitchell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wayne
authors.forename: Kuldeepsinh
authors.initials: K
authors.lastname: Rana
authors.forename: Chris B
authors.initials: CB
authors.lastname: Schaffer
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D012709:Serum Albumin / Q000378:metabolism; D033081:Shear Strength; D013314:Stress, Mechanical; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D019040:E-Selectin; D008081:Liposomes; D012709:Serum Albumin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
keywords: drug delivery; nanomedicine