title: Tungsten-induced carcinogenesis in human bronchial epithelial cells.
abstract: Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans.
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Freda
authors.initials: F
authors.lastname: Laulicht
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Brocato
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Cartularo
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Vaughan
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kluz
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Genome Technology Center, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Betul Akgol
authors.initials: BA
authors.lastname: Oksuz
authors.affiliation: Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Peana
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
authors.forename: Serenella
authors.initials: S
authors.lastname: Medici
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zoroddu
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA. Electronic address: Max.Costa@nyumc.org.
authors.forename: Max
authors.initials: M
authors.lastname: Costa
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D017973:Tungsten Compounds / Q000633:toxicity*
chemical_list: D017973:Tungsten Compounds; C045951:tungstate
keywords: Beas-2B; Cancer; In vitro; Nude mice; RNA-Seq; Tungsten