Cooperative behaviour and phenotype plasticity evolve during melanoma progression

Area of Science:

• Oncology
• Cell Biology
• Genetics

Background:

• Melanoma management is challenged by tumor heterogeneity arising from co-existing melanoma cell phenotypes.
• These distinct phenotypes exhibit variable responses to therapies and drive melanoma progression.
• Phenotypic plasticity, driven by transcriptional reprogramming, is implicated in melanoma progression, but inter-phenotype interactions remain unclear.

Purpose of the Study:

• To investigate the dynamics of melanocytic and mesenchymal phenotypes during melanoma progression.
• To elucidate the interaction patterns between different melanoma cell phenotypes.
• To identify potential therapeutic targets based on inter-phenotype communication.

Main Methods:

• Monitoring of melanocytic and mesenchymal phenotypes throughout melanoma progression.
• Analysis of transcriptional reprogramming at various disease stages.
• Investigation of phenotype interactions and their impact on tumor fitness and metastasis.

Main Results:

• Transcriptional reprogramming occurs at different stages, with mesenchymal traits in circulating melanoma cells (CTCs) and proliferative features in metastases.
• Distinct melanoma phenotype populations interact cooperatively, increasing tumor 'fitness,' supporting CTCs, and enhancing organotropic metastasis.
• Fibronectin, expressed by mesenchymal cells, is crucial for this cooperativity, promoting melanocytic cell survival.

Conclusions:

• Inter-phenotype communication plays a significant role in melanoma progression at multiple stages.
• Cooperative interactions between melanoma phenotypes enhance tumor aggressiveness and metastatic potential.
• Targeting inter-phenotype communications presents a promising therapeutic strategy for melanoma management.