title: E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis.
abstract: Circulating prostate cancer (PCa) cells preferentially roll and adhere on bone marrow vascular endothelial cells, where abundant E-selectin and stromal cell-derived factor 1 (SDF-1) are expressed, subsequently initiating a cascade of activation events that eventually lead to the development of metastases. To elucidate the roles of circulating PCa cells' rolling and adhesion behaviors in cancer metastases, we applied a dynamic cylindrical flow-based microchannel device that is coated with E-selectin and SDF-1, mimicking capillary endothelium. Using this device we captured a small fraction of rolling PCa cells. These rolling cells display higher static adhesion ability, more aggressive cancer phenotypes and stem-like properties. Importantly, mice received rolling PCa cells, but not floating PCa cells, developed cancer metastases. Genes coding for E-selectin ligands and genes associated with cancer stem cells and metastasis were elevated in rolling PCa cells. Knock down of E-selectin ligand 1(ESL-1), significantly impaired PCa cells' rolling capacity and reduced cancer aggressiveness. Moreover, ESL-1 activates RAS and MAP kinase signal cascade, consequently inducing the downstream targets. In summary, circulating PCa cells' rolling capacity contributes to PCa metastasis, and that is in part controlled by ESL-1.
authors.affiliation: Departments of Urology and Pathology and Laboratory Medicine, and Chemical Engineering, University of Rochester, Rochester, NY 14642.
authors.forename: Sayeda
authors.initials: S
authors.lastname: Yasmin-Karim
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853.
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
authors.affiliation: Departments of Urology and Pathology and Laboratory Medicine, and Chemical Engineering, University of Rochester, Rochester, NY 14642.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Messing
authors.affiliation: Departments of Urology and Pathology and Laboratory Medicine, and Chemical Engineering, University of Rochester, Rochester, NY 14642.
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Lee
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor