title: Hodgkin lymphoma cell lines bind to platelets. Incubation with platelets induces CD15 and P-selectin dependent adhesion of the cell lines to Human Umbilical Vein Endothelial cells (HUVEC).
abstract: Hodgkin's lymphoma is believed to spread in an orderly fashion within the lymphatic compartment. In a minority of cases, after reaching the spleen, the neoplasm disseminates, reminiscent of metastasis. In the spleen, the Hodgkin-Reed-Sternberg tumor cells come across platelets in the blood vessels and mainly in the splenic red pulp. Based on this knowledge, we investigated the possibility of platelets inducing cell adhesion in Hodgkin's lymphoma cell lines. We showed that L428 and KMH-2 cells strongly adhere to thrombin-activated platelets. Cell adhesion to platelets is partially dependent on CD15 antigens (Lewis(X)), mainly sialyl-CD15, and P-selectin. KMH-2, as compared to L428 cells, showed increased binding due to its differential high expression of the sialyl-CD15. As a consequence of incubation with platelets, KMH-2 cells also produced increased amounts of tumor necrosis factors α (TNFα) followed by enhanced binding to human vascular endothelial cells (HUVEC). Incubation of both cell lines with activated platelets also induced activation of AP-1 transcription complex. Our findings are consistent with the concept that platelets play a critical role in the dissemination of HRS cells in HL, predominantly in the spleen, by increasing cell adhesion and thus promoting their proliferative and migratory properties beyond the lymphatic system.
authors.affiliation: a Department of Microbiology ; Immunology and Genetics; Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.
authors.forename: Ofra Malka
authors.initials: OM
authors.lastname: Ohana
authors.affiliation: a Department of Microbiology ; Immunology and Genetics; Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.
authors.forename: Janet
authors.initials: J
authors.lastname: Ozer
authors.affiliation: b Department of Pathology ; Soroka University Medical Center; and Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.
authors.forename: Isebrand
authors.initials: I
authors.lastname: Prinsloo
authors.affiliation: b Department of Pathology ; Soroka University Medical Center; and Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.|d These authors contributed equally to this work.
authors.forename: Daniel
authors.initials: D
authors.lastname: Benharroch
authors.affiliation: a Department of Microbiology ; Immunology and Genetics; Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.|c Department of Oncology ; Soroka University Medical Center; and Faculty of Health Sciences; Ben Gurion University of the Negev ; Beer-Sheva , Israel.|d These authors contributed equally to this work.
authors.forename: Jacob
authors.initials: J
authors.lastname: Gopas
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005647:Fucosyltransferases / Q000378:metabolism*; D006031:Glycosylation; D006689:Hodgkin Disease / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism*; D015539:Platelet Activation; D011499:Protein Processing, Post-Translational; D013917:Thrombin / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016256:Lewis X Antigen; D019007:P-Selectin; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C066693:FUT4 protein, human; D005647:Fucosyltransferases; D013917:Thrombin; D019158:N-Acetylneuraminic Acid
keywords: CD15; Hodgkin lymphoma; LewisX; P selectin; metastasis; platelet-induced adhesion; thrombin-activated platelets