A novel algorithmic approach to simulating cell-cell interactions in lung cancer initiation #

Helena Coggan, Philip Pearce, Mohit Dalwadi, Clare Weeden, Karen Page, Charles Swanton

11:50 Monday in 3Q68.

Part of the Cell modelling session.

Abstract #

Many genetic mutations are known to be associated with cancer, but their mechanisms of action in the human body are unclear. To gain fundamental insight, we focus on a particular mutation (EGFR-L858R) associated with lung cancer in never-smokers. Experiments show that cell clusters with this mutation exhibit unexpected “bubbling” structures when cultured in vitro, suggesting that cell-cell interactions are perturbed. In this presentation, I will describe how we use a novel on-lattice agent-based model to investigate which cell-cell interactions are required to form the emergent morphology of the cell clusters. The model reveals a nonlinear form of cell-cell interaction in which mutant cells act to suppress the proliferation of their neighbours, suggesting a new hypothesis for the emergence of invasive carcinomas with this mutation. I will show how our algorithm can be adapted to incorporate other processes (differentiation, senescence, nutrient absorption, etc.). Our work demonstrates the importance of computationally cheap, minimally-parameterised models in uncovering the mechanisms of cancer initiation.