title: Extracellular DNA: A Bridge to Cancer.
abstract: DNase I is a secreted enzyme whose function has been presumed to control "waste management" in the human system, by degrading DNA that leaks from dead and dying cells. Emerging studies have instead yielded evidence that DNase I plays a central role in newly defined dynamics of immune and autoimmune diseases, as well as cancer and vascular disorders, including thrombosis. Cancer cells have been reported to be associated with distinctive extracellular structures that facilitate aggregation and implantation. The fact that DNA is a component of such structures and that it plays a role in cancer development is illustrated by direct evidence: DNase I added to tumor cells eliminates the structures and inhibits tumorigenicity of some cancer cell lines. DNase I injected into experimental animals, moreover, results in significant inhibition of metastasis. Despite independent observations of such phenomena in diverse cancers for over 50 years, the potential for using DNase I as a clinical tool to prevent or treat cancer remains unexplored. The discovery of neutrophil extracellular traps has yielded a conceptual framework for interpreting how extracellular DNA may function in cancer development and why it may prove to be an important clinical target in stopping cancer outside the cell.
authors.affiliation: Department of Soil, Water, and Environmental Sciences, Bio5 Institute of Life Sciences, University of Arizona, Tucson, Arizona. mhawes@email.arizona.edu.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Hawes
authors.affiliation: Ventana Medical Systems, Inc., Roche Tissue Diagnosis, Oro Valley, Arizona.
authors.forename: Fushi
authors.initials: F
authors.lastname: Wen
authors.affiliation: Arizona Cancer Center, Division of Hematology/Oncology, University of Arizona, Tucson, Arizona.
authors.forename: Emad
authors.initials: E
authors.lastname: Elquza
mesh_terms: D016022:Case-Control Studies; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D005110:Extracellular Space / Q000235:genetics / Q000378:metabolism; D065206:Extracellular Traps / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism*
chemical_list: D004247:DNA; D003851:Deoxyribonucleases; D003850:Deoxyribonuclease I