title: Industasis, a promotion of tumor formation by nontumorigenic stray cells.
abstract: A tumor cell is formed when a critical amount of endogenous and/or exogenous tumorigenic stimuli is exceeded. We have shown that the transient presence of nontumorigenic stray cells in tissues of experimental animals that contain cells with a subcritical set of genetic mutations can act as a tumor-promoting stimulus. To induce somatic mutations in all chicken tissues, we have used the MAV-2 retroviral insertion system that almost exclusively generates nephroblastomas. MAV-2 mutagenized animals i.v. inoculated with nonmalignant cells developed early clonal lung tumors before nephroblastomas. Importantly, the injected cells did not become a component of resultant tumors. Lung tumors displayed specific mutational signature characterized by an insertion of MAV-2 provirus into the fyn-related kinase (frk) promoter that results in the overexpression of the frk gene. In contrast, plag1, foxP, and twist genes were most often mutagenized in nephroblastomas. Based on such observations, we propose the mechanism termed industasis, a promotion of fully malignant phenotype of incipient tumor cell by stray cells, and hypothesize that it might be the underlying cause of human multiple primary tumors.
authors.affiliation: Institute of Molecular Genetics AS CR, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Pajer
authors.forename: Vít
authors.initials: V
authors.lastname: Karafiát
authors.forename: Vladimír
authors.initials: V
authors.lastname: Pecenka
authors.forename: Dana
authors.initials: D
authors.lastname: Pruková
authors.forename: Jana
authors.initials: J
authors.lastname: Dudlová
authors.forename: Jirí
authors.initials: J
authors.lastname: Plachy
authors.forename: Petra
authors.initials: P
authors.lastname: Kasparová
authors.forename: Michal
authors.initials: M
authors.lastname: Dvorák
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002477:Cells / Q000473:pathology* / Q000821:virology; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D007680:Kidney Neoplasms / Q000473:pathology / Q000821:virology; D008175:Lung Neoplasms / Q000473:pathology / Q000821:virology; D008954:Models, Biological; D016254:Mutagenesis, Insertional / Q000502:physiology; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary / Q000209:etiology; D011533:Proviruses / Q000254:growth & development / Q000502:physiology; D018406:Virus Physiological Phenomena; D009396:Wilms Tumor / Q000473:pathology / Q000821:virology