title: Uveal melanoma expresses NK-1 receptors and cyclosporin A induces apoptosis in human melanoma cell lines overexpressing the NK-1 receptor.
abstract: Substance P and neurokinin-1 (NK-1) receptor antagonists respectively induce proliferation and growth inhibition in human melanoma cell lines. The presence of NK-1 receptors in human melanoma cell lines and samples has been reported, but the presence of NK-1 receptors has not been demonstrated in uveal melanomas. It is known that melanoma express the tachykinin 1 receptor (TAC1R) gene. This gene is overexpressed in several human cancer cell lines, but such overexpression is currently unknown in human malignant melanoma cell lines (COLO 858, MEL HO, COLO 679). In this study, we attempt to demonstrate the overexpression of the TAC1R gene in such cells. We performed an in vitro study by real-time quantitative RT-PCR for TAC1R and found that the NK-1 receptor was overexpressed in the three human melanoma cell lines studied. Using a knockdown method, we demonstrate that the NK-1 receptor is involved in the viability of the COLO 858 melanoma cell line. Immunohistochemistry was also used to demonstrate NK-1 receptors in uveal melanoma samples. We observed that NK-1 receptors were present in the 21/21 uveal melanomas. In addition, cyclosporin A inhibited the growth of the three melanoma cell lines studied in a dose-dependent manner, and after the administration of this immunosuppresive drug apoptosis was observed. This indicates at least that the antitumor action of cyclosporin A is mediated by the NK-1 receptor. Our findings suggest that the NK-1 receptor could be a promising target in the treatment of human melanomas.
authors.affiliation: Vírgen del Rocío University Hospital, Research Laboratory on Neuropeptides Sevilla, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Ortega
authors.affiliation: Vírgen del Rocío University Hospital, Research Laboratory on Neuropeptides Sevilla, Spain.
authors.forename: Elia
authors.initials: E
authors.lastname: Sánchez-Vaderrábanos
authors.affiliation: Vírgen del Rocío University Hospital, Research Laboratory on Neuropeptides Sevilla, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Ramiro-Fuentes
authors.affiliation: Hospital Juan Ramón Jiménez, Huelva, Spain.
authors.forename: Manuel Vicente
authors.initials: MV
authors.lastname: Salinas-Martín
authors.affiliation: Deparment of Pathology, "Vírgen del Rocío" University Hospital, Sevilla, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Carranza
authors.affiliation: Institute of Neurosciences of Castilla y León (INCYL) , Laboratory of Neuroanatomy of the Peptidergic Systems, Laboratory 14, Salamanca, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coveñas
authors.affiliation: Vírgen del Rocío University Hospital, Research Laboratory on Neuropeptides Sevilla, Spain. Electronic address: mmunoz@cica.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D016572:Cyclosporine / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult; D000098943:Uveal Melanoma
chemical_list: D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D016572:Cyclosporine
keywords: Apoptosis; COLO 679; COLO 858; Cyclosporin A; MEL HO; NK-1 receptor; Substance P; TAC1R; Uveal melanoma