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Growth and metastasis in melanoma are decoupled by a cellular hierarchy

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Published By:
Peeyush Ghalot
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Published On:
28-09-2022
(Photo Courtesy: - Mayo Lab)

Although melanoma is well known for having significant levels of heterogeneity and plasticity1,2, it is still unclear where and how much cell-state variety exists. It is also unknown if overlapping or different melanoma subpopulations enable growth and metastatic dissemination. Here, using a combination of mouse genetics, single-cell and spatial transcriptomics, lineage tracing, and quantitative modeling, we demonstrate evidence of a hierarchical model of tumour growth that mimics the cellular and molecular logic underlying the cell-fate specification and differentiation of the embryonic neural crest. We demonstrate that a spatially localised perivascular niche—a feature acquired through an intercellular communication pathway formed by endothelial cells—is related with tumorigenic competence. Temporal single-cell tracing of a population of melanomas cells in a mesenchymal-like state revealed that these cells do not contribute to the growth of the primary tumor but rather form a pool of metastatic initiating cells that switch cell identities while spreading to secondary organs, which is consistent with a model in which only a portion of cells are fated to fuel growth. The information suggests that only specific cell pools have the capacity to promote growth and metastasis and provides a geographically and time defined map of the diversity and dynamics of melanoma cell states. The finding that certain phenotypic skills can be dynamically gained following exposure to particular niche signals justifies the development of treatment approaches that block the reprogramming activity of such microenvironmental cues on cancer cells.

Reference: - https://pubmed.ncbi.nlm.nih.gov/36131018/