title: Mathematical model of the role of intercellular signalling in intercellular cooperation during tumorigenesis.
abstract: OBJECTIVE
  Intercellular cooperation has been hypothesized to enhance cell proliferation during cancer metastasis through autocrine signalling cascades and mathematical models can provide valuable insights into underlying mechanisms of metastatic tumorigenesis. Here, we present a model that incorporates signal-stimulated cell proliferation, and investigate influences of diffusion-driven heterogeneity in signal concentration on proliferation dynamics.
  
  
  METHODS
  Our model incorporates signal production through both autocrine and paracrine pathways, and signal diffusion and loss for a metastasizing cell population at a host site. We use the signalling pathway of IL-6 for illustration where this signalling species forms an intermediate complex with its receptor IL-6R. This in turn forms a heterodimeric complex with transmembrane protein gp130, ultimately resulting in production of downstream signals. Cell population dynamics are taken to follow a modified logistic equation for which the rate term is dependent on local IL-6 concentration.
  
  
  CONCLUSIONS
  Our spatiotemporal model agrees closely with experimental results. The model is also able to predict two phenomena typical of metastatic tumorigenesis - host tissue preference and long periods of proliferation dormancy. It confirms that diffusivity of the signalling species in a host tissue plays a significant role during the process. Our results show that the proliferation-apoptosis balance is tipped in favour of the former for host sites that have relatively smaller signal diffusivities.
authors.affiliation: Department of Engineering Science and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Elankumaran
authors.forename: I K
authors.initials: IK
authors.lastname: Puri
mesh_terms: D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009362:Neoplasm Metastasis; D019947:Receptors, Interleukin-6 / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130