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. 2021 Feb 4;10:626129. doi: 10.3389/fonc.2020.626129

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Copyright © 2021 Eddy, Shah and Chen

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Melanoma Metastasis. Three routes of primary melanoma dissemination are outlined. A primary melanoma can undergo 1) passive shedding of tumor cells, non-EMT (epithelial to mesenchymal transition) followed by passive intravasation, 2) tumor cells can undergo EMT and active intravasation or 3) melanoma cells can undergo EMT and bring along non-EMT tumor cells, where the EMT cells are actively intravasating while the non-EMT cell are undergoing passive intravasation. Once in circulation, tumor cells will migrate to site of metastasis. If the tumor cells are active, they will undergo the canonical extravasation by mesenchymal to epithelial transition (MET). If the tumor cells are dormant, they will transdifferentiate into endothelial cells at the intravascular niche, undergo endothelial to mesenchymal transition (EndMT) and extravasate into the niche. Created with BioRender.com.