Adipocyte-derived lipids promote phenotypic bistability in a structured population model for melanoma growth

KeithChambers

University of Oxford

"Adipocyte-derived lipids promote phenotypic bistability in a structured population model for melanoma growth"

Melanoma cells exhibit a continuum of proliferative to invasive phenotypes. While single-cell and spatial transcriptomics have enabled biologists to quantify the distribution of phenotype amongst melanoma cells, a complete mechanistic understanding is currently lacking. A key issue is the impact of adipocyte-derived lipids, whose uptake by melanoma cells drives an invasive response that may lead to metastasis. To address this, we have developed a phenotype-structured model for melanoma cell populations that couples the phenotype dynamics to the essential aspects of intracellular lipid metabolism and the extracellular microenvironment. In this talk, I will first introduce a single-cell ODE model that illustrates how lipid uptake gives rise to phenotypic bistability in melanoma cells. I will then show how a phenotype-structured population model, whose advection term is informed by the single-cell model, exhibits a range of qualitative behaviours, including cyclic solutions and bimodal phenotypic distributions. Together, these results increase understanding of the role played by adipocyte-derived lipids and other microenvironment factors in shaping the distribution of phenotype in melanoma cell populations. We speculate that our modelling framework may also be applicable to other lipid-rich tumours (e.g. breast and ovarian cancers) that are commonly associated with increased metastasis.
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