A computational model of organism development and carcinogenesis resulting from cells’ bioelectric properties and communication

" The simple model proposed in this work allows also to address the carcinogenesis problem, by using premises from the Tissue Organization Field Theory (TOFT) [31]. The excessive, poorly controlled and non-homeostatic cell proliferation can be due to a deregulation of the tissue bioelectric state, a consequence of depolarization events. This non-mutagenic incident [32,33,34] implies that carcinogenesis can be due to a failure on tissue organization process and not the result of an individual cell failure, with cell mutations being a consequence rather than the cancer cause [35]. The cells’ bioelectric state was shown, by several experimental tests, to have influence in carcinogenesis and in cancer therapy [36], with the most relevant factors being the transmembrane electric potential and the conductance through ion channels. A study about the connection between cancer hallmarks and ion channels pathologies was published [37], showing that gap junctions’ performance is relevant in tumor development, in particular its long-range control [38]." {Credits 1}

" Alexis Pietak and Michael Levin [40] describe how bioelectricity can be integrated in genetic and reaction networks, where V m can change the concentrations of key signaling molecules, both inside and outside the cells." {Credits 1}

" Many experimental observations point out to the importance of bioelectricity in organism development and regeneration, supporting the conclusion that the tissue’s bioelectric state is fundamental for a correct organism development." {Credits 1}

" The present model, when applied to tumor initiation, is related to the Tissue Organization Field Theory (TOFT) [31,45], as it deals with the emergence of tissue organization at a supra cellular level, and cancer is considered a disease of tissue homeostasis regulation, not initiated from an individual cell pathological behavior but a tissue organization breakdown. Accordingly, a tumor originates from a perturbation on tissue environment and reciprocal interactions between parenchyma and stroma, not from a single mutated cell, leading to a transition from an organized to disorganized state. In this work, intercellular communication by bioelectric signals is a mechanism driving homeostasis at tissue level; however, after an extensive perturbation, the tissue bioelectric state can change and the cells’ properties be modified. ... The excessive cell proliferation creates adverse conditions for cells’ survival, which includes a decrement in nutrient concentration, hypoxia and reduced pH, promoting DNA damage, stimulating genetic mutations and reducing DNA’s repair capability [47,48]." {Credits 1}

{Credits 1} 🎪 Carvalho, J. A computational model of organism development and carcinogenesis resulting from cells’ bioelectric properties and communication. Sci Rep 12, 9206 (2022). © 2022 The Author(s). This is an open access article distributed under the Creative Commons Attribution International License.