title: Senescent bronchial fibroblasts induced to senescence by Cr(VI) promote epithelial-mesenchymal transition when co-cultured with bronchial epithelial cells in the presence of Cr(VI).
abstract: Cellular senescence is a physiological process that serves as a powerful barrier for tumorigenesis. However, senescent cells can be deleterious for the tissue microenvironment. Such is the case of senescent fibroblasts that release several pro-tumorigenic factors that promote malignant transformation in the nearby epithelial cells. Occupational exposure to hexavalent chromium [Cr(VI)] compounds is a cause of respiratory cancers. Although Cr(VI) is known to induce senescence in human foreskin fibroblasts, the role of senescent fibroblasts in the Cr(VI)-induced malignant transformation of human bronchial epithelial cells was never assessed. Thus, to study the evolutionary dynamics generated by the interaction between human bronchial epithelial cells and senescent bronchial fibroblasts, the non-tumorigenic human bronchial epithelial BEAS-2B cells were co-cultured with Cr(VI)-induced senescent human bronchial fibroblasts for 4 weeks. Under the pressure of 0.5 µM Cr(VI), senescent fibroblasts promoted the acquisition of mesenchymal features on BEAS-2B cells, e.g. the fusiform shape and increased Vimentin expression, consistent with the occurrence of an epithelial-mesenchymal transition-like process. Features of transformed cells including larger nuclei, as well as nuclei with heterogeneous size, were also observed. Altogether the results obtained demonstrate that besides acting over the epithelium, Cr(VI) also affects bronchial fibroblasts driving them senescent. As a consequence, a paracrine communication loop is established with the above-placed epithelium prompting the epithelial cells for malignant transformation and thus facilitating the initial steps of tumorigenesis.
authors.affiliation: Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal, Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Center for Neuroscience and Cell Biology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal and.
authors.forename: Mariana Monteiro
authors.initials: MM
authors.lastname: Val
authors.affiliation: Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal, Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Center for Neuroscience and Cell Biology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal and.
authors.forename: Luís André
authors.initials: LA
authors.lastname: Mendes
authors.affiliation: Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Alarcão
authors.affiliation: Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Lina
authors.initials: L
authors.lastname: Carvalho
authors.affiliation: Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Center for Neuroscience and Cell Biology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal and Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Carreira
authors.affiliation: Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Center for Neuroscience and Cell Biology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal and Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Carlos Fernando D
authors.initials: CF
authors.lastname: Rodrigues
authors.affiliation: Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal, Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal, Center for Neuroscience and Cell Biology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal and mcalpoim@bioq.uc.pt.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Alpoim
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D002857:Chromium / Q000633:toxicity*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans
chemical_list: D002857:Chromium; C074702:chromium hexavalent ion