"Evolution, regulation and disruption of homeostasis and its role in carcinogenesis", A.R.A. Anderson, D. Basanta, P. Gerlee, K.A. Rejniak in Multiscale Cancer Modeling
Abstract: At its simplest tissue homeostasis is the balance between cell proliferation and apoptosis that preserves the architecture and functionality of a tissue. It is estimated that 50 to 70 billion cells are dying every day in an average adult and approximately the same number of cells need to be born to keep body integrity. This balance is maintained by multiple subcellular, intracellular and extracellular mechanisms including cell genetic management, cell-cell adhesion, paracrine/autocrine signaling, and cell-ECM interactions. The process of carcinogenesis entails the escape from these mechanisms, and the evolution of the tumour cell population towards phenotypes that can exploit or become independent of the normal tissue microenvironmental constraints. In this chapter we consider the mechanisms which regulate normal tissue homeostasis and subsequently homeostatic escape in the development of cancer by using different modelling approaches that examine the roles played by physical constraints, cell-microenvironment interactions and evolutionary dynamics. |