title: Cancer progression mediated by horizontal gene transfer in an in vivo model.
abstract: It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy.
authors.affiliation: Division of Basic Research, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Catalina
authors.initials: C
authors.lastname: Trejo-Becerril
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Cárdenas
authors.forename: Lucía
authors.initials: L
authors.lastname: Taja-Chayeb
authors.forename: Philippe
authors.initials: P
authors.lastname: Anker
authors.forename: Roberto
authors.initials: R
authors.lastname: Herrera-Goepfert
authors.forename: Luis A
authors.initials: LA
authors.lastname: Medina-Velázquez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.forename: Delia
authors.initials: D
authors.lastname: Pérez-Montiel
authors.forename: Alma
authors.initials: A
authors.lastname: Chávez-Blanco
authors.forename: Judith
authors.initials: J
authors.lastname: Cruz-Velázquez
authors.forename: José
authors.initials: J
authors.lastname: Díaz-Chávez
authors.forename: Miguel
authors.initials: M
authors.lastname: Gaxiola
authors.forename: Alfonso
authors.initials: A
authors.lastname: Dueñas-González
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D018628:Gene Dosage; D022761:Gene Transfer, Horizontal; D011905:Genes, ras; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D051381:Rats; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; C101860:RAB30 protein, human; D020691:rab GTP-Binding Proteins