title: Circulating tumor cells from prostate cancer patients interact with E-selectin under physiologic blood flow.
abstract: Hematogenous metastasis accounts for the majority of cancer-related deaths, yet the mechanism remains unclear. Circulating tumor cells (CTCs) in blood may employ different pathways to cross blood endothelial barrier and establish a metastatic niche. Several studies provide evidence that prostate cancer (PCa) cell tethering and rolling on microvascular endothelium via E-selectin/E-selectin ligand interactions under shear flow theoretically promote extravasation and contribute to the development of metastases. However, it is unknown if CTCs from PCa patients interact with E-selectin expressed on endothelium, initiating a route for tumor metastases. Here we report that CTCs derived from PCa patients showed interactions with E-selectin and E-selectin expressing endothelial cells. To examine E-selectin-mediated interactions of PCa cell lines and CTCs derived from metastatic PCa patients, we used fluorescently-labeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591-488 which is internalized following cell-surface binding. We employed a microscale flow device consisting of E-selectin-coated microtubes and human umbilical vein endothelial cells (HUVECs) on parallel-plate flow chamber simulating vascular endothelium. We observed that J591-488 did not significantly alter the rolling behavior in PCa cells at shear stresses below 3 dyn/cm(2). CTCs obtained from 31 PCa patient samples showed that CTCs tether and stably interact with E-selectin and E-selectin expressing HUVECs at physiological shear stress. Interestingly, samples collected during disease progression demonstrated significantly more CTC/E-selectin interactions than samples during times of therapeutic response (p=0.016). Analysis of the expression of sialyl Lewis X (sLe(x)) in patient samples showed that a small subset comprising 1.9-18.8% of CTCs possess high sLe(x) expression. Furthermore, E-selectin-mediated interactions between prostate CTCs and HUVECs were diminished in the presence of anti-E-selectin neutralizing antibody. CTC-Endothelial interactions provide a novel insight into potential adhesive mechanisms of prostate CTCs as a means to initiate metastasis.
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Gakhar
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Vicente N
authors.initials: VN
authors.lastname: Navarro
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Madelyn
authors.initials: M
authors.lastname: Jurish
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Guang Yu
authors.initials: GY
authors.lastname: Lee
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America ; Department of Urology, Weill Cornell Medical College, New York, New York, United States of America ; Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Naveed H
authors.initials: NH
authors.lastname: Akhtar
authors.affiliation: Department of Surgery, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Seandel
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York, United States of America ; Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America ; Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Giannakakou
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
authors.affiliation: Deparment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York, United States of America ; Department of Urology, Weill Cornell Medical College, New York, New York, United States of America ; Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
mesh_terms: D001783:Blood Flow Velocity; D002460:Cell Line; D019040:E-Selectin / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D013312:Stress, Physiological
chemical_list: D019040:E-Selectin; D009363:Neoplasm Proteins