The human melanoma cell line MelJuSo secretes bioactive FasL and APO2L/TRAIL on the surface of microvesicles. Possible contribution to tumor counterattack

• Published in: Experimental cell research Vol. 295; no. 2; pp. 315 - 329
• Main Authors: Martı́nez-Lorenzo, Marı́a José, Anel, Alberto, Alava, Marı́a A, Piñeiro, Andrés, Naval, Javier, Lasierra, Pilar, Larrad, Luis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2004
• Subjects: Actins - metabolism; alpha-MSH - pharmacology; Apoptosis; Apoptosis Regulatory Proteins; Cell Division; Cell Line, Tumor; Cell Survival; Coculture Techniques; Cytotoxicity Tests, Immunologic; fas Receptor - immunology; fas Receptor - metabolism; Human; Humans; Intracellular Membranes - physiology; Jurkat Cells; Ligands; Lymphocyte Activation; Melanoma - immunology; Melanoma - metabolism; Melanoma - pathology; Membrane Glycoproteins - secretion; Membrane Potentials - drug effects; Microtubules - metabolism; Mitochondria - physiology; Phytohemagglutinins - pharmacology; Secretory Vesicles - drug effects; Secretory Vesicles - immunology; Secretory Vesicles - metabolism; Secretory Vesicles - ultrastructure; T-Lymphocytes - cytology; T-Lymphocytes - immunology; TNF-Related Apoptosis-Inducing Ligand; Tumor immunity; Tumor Necrosis Factor-alpha - secretion; Human; IEM; Tumor immunity; APO2L; FasL; DiOC 6; α-MSH; Apoptosis; ΔΨ m
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2003.12.024

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 α-melanocyte stimulating hormone (α-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.