Modelling the interplay of physical and chemical drivers of tumour metastasis

Fabian Spill (University of Birmingham)

Thursday 27th February, 2020 14:00-15:00 Maths 311B

Abstract

Cancer mostly kills through metastasis - the process where cancer cells leave the primary tumour and colonialize distant organs. Such movement of cells naturally requires forces. How cells generate forces through molecular pathways is thus an intense field of study. Moreover, it is becoming increasingly appreciated that forces, and other physical properties, not only arise from intracellular pathways, but can also affect pathways, for instance, through cellular mechanosensors. I will present several mathematical models developed to understand this complex interplay of mechanical and chemical regulation of cells.

First, I will introduce a model of an endothelial cell monolayer that can predict the dynamic formation of gaps in the layer. These gaps arise due to forces that change the chemical binding rates of cell-cell adhesions. Experiments show that these gaps can be exploited by cancer cells when transmigrating through the endothelium - a crucial process during metastasis.

I will then show some past and ongoing work on modelling mechano-chemical pathways in cells. Pathways including the YAP/TAZ and Rho signalling pathways are sensitive e.g. to extrinsic factors such as extracellular stiffness, or intrinsic factors such as cellular geometry. The complex interplay of such factors can lead to reprogramming of cells. Consequently, a physically altered tumour environment can activate intracellular pathways and, independent or complementary to genetic changes, alter tumour cells towards more aggressive behaviour.

References:

https://doi.org/10.1371/journal.pcbi.1006395

https://doi.org/10.1016/j.csbj.2018.07.002

https://doi.org/10.1088/1478-3975/13/3/036008

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