title: Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis.
abstract: Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy.
authors.affiliation: Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, B1650KNA, Argentina.|Consejo Nacional de Investigaciones Científicas y Tecnológicas, Buenos Aires, C1033AAJ, Argentina.
authors.forename: Candelaria
authors.initials: C
authors.lastname: Bracalente
authors.affiliation: Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, B1650KNA, Argentina.
authors.forename: Noelia
authors.initials: N
authors.lastname: Salguero
authors.affiliation: Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, B1650KNA, Argentina.
authors.forename: Cintia
authors.initials: C
authors.lastname: Notcovich
authors.affiliation: Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035 003, Brasil.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Müller
authors.affiliation: Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035 003, Brasil.
authors.forename: Leonardo L
authors.initials: LL
authors.lastname: da Motta
authors.affiliation: Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035 003, Brasil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Klamt
authors.affiliation: Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, B1650KNA, Argentina.|Consejo Nacional de Investigaciones Científicas y Tecnológicas, Buenos Aires, C1033AAJ, Argentina.
authors.forename: Irene L
authors.initials: IL
authors.lastname: Ibañez
authors.affiliation: Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires, B1650KNA, Argentina.|Consejo Nacional de Investigaciones Científicas y Tecnológicas, Buenos Aires, C1033AAJ, Argentina.|Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires, B1650HMP, Argentina.
authors.forename: Hebe
authors.initials: H
authors.lastname: Durán
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics*; D054337:Cell Dedifferentiation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D002999:Clone Cells; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D018328:Melanoma, Amelanotic / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D008543:Melanins; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: ROS; catalase; melanogenesis and metastasis; melanoma