Industasis, a promotion of tumor formation by nontumorigenic stray cells

0333751 - ÚMG 2010 RIV US eng J - Journal Article
Pajer, Petr - Karafiát, Vít - Pečenka, Vladimír - Průková, Dana - Dudlová, J. - Plachý, Jiří - Kašparová, P. - Dvořák, Michal
Industasis, a promotion of tumor formation by nontumorigenic stray cells.
Cancer Research. Roč. 69, č. 11 (2009), s. 4605-4612. ISSN 0008-5472. E-ISSN 1538-7445
R&D Projects: GA ČR GA204/06/1728; GA MŠMT(CZ) LC06061; GA AV ČR IAA500520608
Institutional research plan: CEZ:AV0Z50520514
Keywords : tumor promotion * lung tumors * Fyn-related kinase
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.543, year: 2009

We have demonstrated that transient presence of non-tumorigenic stray cells in tissues of experimental animals containing cells with a sub-critical set of genetic mutations can act as a tumor-promoting stimulus. To induce somatic mutations in all chicken tissues we used MAV-2 retroviral insertion system almost exclusively generating nephroblastomas. MAV-2 mutagenized animals inoculated with non-malignant cells developed early clonal lung tumors prior to nephroblastomas. Importantly, injected cells did not become a component of resultant tumors. Lung tumors displayed specific mutational signature characterized by insertion of MAV-2 provirus into frk promoter resulting in over-expression of gene frk. In contrast, plag1, foxP1 and twist genes were most often mutagenized in nephroblastomas. 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 a cause of human multiple primary tumors.
Permanent Link: http://hdl.handle.net/11104/0178669