title: Mechanistic modelling suggests that the size of preneoplastic lesions is limited by intercellular induction of apoptosis in oncogenically transformed cells.
abstract: Selective removal of oncogenically transformed cells by apoptosis induced via signalling by surrounding cells has been suggested to represent a natural anticarcinogenic process. To investigate its potential effect in detail, a mechanistic model of this process is proposed. The model is calibrated against in vitro data on apoptosis triggered in transformed cells by defined external inducers as well as through signalling by normal cells under coculture conditions. The model predicts that intercellular induction of apoptosis is capable of balancing the proliferation of oncogenically transformed cells and limiting the size of their populations over long times, even if their proliferation per se were unlimited. Experimental research is desired to verify whether the predicted stable population of transformed cells corresponds to a kind of dormancy during early-stage carcinogenesis (dormant preneoplastic lesions), and how this process relates to other anticarcinogenic mechanisms taking place under in vivo conditions.
authors: Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Radiation Protection, Neuherberg, Germany. pavel.kundrat@helmholtz-muenchen.de
authors: Pavel
authors: P
authors: Kundrát
authors: Georg
authors: G
authors: Bauer
authors: Peter
authors: P
authors: Jacob
authors: Werner
authors: W
authors: Friedland
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology*; D018920:Coculture Techniques; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006997:Hypochlorous Acid / Q000494:pharmacology; D008962:Models, Theoretical; D030421:Peroxynitrous Acid / Q000494:pharmacology; D011230:Precancerous Conditions / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016588:Anticarcinogenic Agents; D030421:Peroxynitrous Acid; D006997:Hypochlorous Acid