Cooperative behaviour and phenotype plasticity evolve during melanoma progression.

Pigment Cell & Melanoma Research
Emily J RowlingClaudia Wellbrock

Abstract

A major challenge for managing melanoma is its tumour heterogeneity based on individual co-existing melanoma cell phenotypes. These phenotypes display variable responses to standard therapies, and they drive individual steps of melanoma progression; hence, understanding their behaviour is imperative. Melanoma phenotypes are defined by distinct transcriptional states, which relate to different melanocyte lineage development phases, ranging from a mesenchymal, neural crest-like to a proliferative, melanocytic phenotype. It is thought that adaptive phenotype plasticity based on transcriptional reprogramming drives melanoma progression, but at which stage individual phenotypes dominate and moreover, how they interact is poorly understood. We monitored melanocytic and mesenchymal phenotypes throughout melanoma progression and detected transcriptional reprogramming at different stages, with a gain in mesenchymal traits in circulating melanoma cells (CTCs) and proliferative features in metastatic tumours. Intriguingly, we found that distinct phenotype populations interact in a cooperative manner, which generates tumours of greater "fitness," supports CTCs and expands organotropic cues in metastases. Fibronectin, expressed in mesenchym...Continue Reading

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Citations

Nov 11, 2020·International Journal of Molecular Sciences·Karol GranadosJochen Utikal
Apr 20, 2021·Cancer Metastasis Reviews·Hendrik Hld VandyckVéronique Winnepenninckx

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Methods Mentioned

BETA
FCS
xenografts
fluorescence imaging

Software Mentioned

GSEA
GraphPad
GraphPad Prism
Incucyte

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