Industasis, a Promotion of Tumor Formation by Nontumorigenic Stray Cells
| Autor: | Jana Dudlova, Vladimír Pecenka, Jirí Plachy, Vít Karafiát, Dana Pruková, Michal Dvorak, Petr Pajer, Petra Kašparová |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Lung Neoplasms Somatic cell Cells Cell Chick Embryo Biology medicine.disease_cause Models Biological Wilms Tumor Neoplasms Multiple Primary Proviruses Cell Movement medicine Animals Neoplasm Invasiveness Gene Mitotic catastrophe Cells Cultured Genetics Kinase Provirus Kidney Neoplasms Mutagenesis Insertional Cell Transformation Neoplastic medicine.anatomical_structure Oncology Cancer research Tumor promotion Carcinogenesis Chickens Virus Physiological Phenomena |
| Zdroj: | Cancer Research. 69:4605-4612 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. [Cancer Res 2009;69(11):4605–12] |
| Databáze: | OpenAIRE |
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