title: The human melanoma cell line MelJuSo secretes bioactive FasL and APO2L/TRAIL on the surface of microvesicles. Possible contribution to tumor counterattack.
abstract: Tumor cells have developed multiple mechanisms to evade control by the immune system. Tumoral cells expressing Fas ligand (FasL) have been proposed to "counterattack" against activated antitumoral effector immune cells, although some authors have indicated that FasL is not expressed on the surface of the same tumors, such in the case of melanoma cells. However, other factors could be implicated, such as the balance of soluble versus membrane-bound forms or the secretion of death ligands on the surface of microvesicles, as described previously by our group in human T cells. In the present study, we analyzed the expression and secretion of FasL and APO2 ligand (APO2L)/TRAIL in the human melanoma cell line MelJuSo. We have observed the expression of preformed FasL and APO2L/TRAIL in these cells, their secretion associated with microvesicles upon melanoma activation with PHA or with alpha-melanocyte stimulating hormone (alpha-MSH), and the toxicity of these microvesicles against normal human T cell blasts. We have also observed that the mechanism of secretion of FasL and APO2L/TRAIL from melanoma cells is depending both on microtubules and actin filaments. From these data, it can be concluded that the MelJuSo melanoma cell line has the possibility to "counterattack" against activated immune effector cells. However, the in vivo outcome seems more complex since it has been also described that FasL expressed in tumors has a proinflammatory effect.
authors.affiliation: Servicio de Inmunología, Hospital Clínico Universitario Lozano Blesa, E-50009, Zaragoza, Spain. linm@hcu-lblesa.es
authors.forename: María José
authors.initials: MJ
authors.lastname: Martínez-Lorenzo
authors.forename: Alberto
authors.initials: A
authors.lastname: Anel
authors.forename: María A
authors.initials: MA
authors.lastname: Alava
authors.forename: Andrés
authors.initials: A
authors.lastname: Piñeiro
authors.forename: Javier
authors.initials: J
authors.lastname: Naval
authors.forename: Pilar
authors.initials: P
authors.lastname: Lasierra
authors.forename: Luis
authors.initials: L
authors.lastname: Larrad
mesh_terms: D000199:Actins / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008870:Microtubules / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D022142:Secretory Vesicles / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
chemical_list: D000199:Actins; D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000521:alpha-MSH