Melanoma, one of the most aggressive
malignancies, its high mortality and low survival rates are associated with effective metastatic colonization.
Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (
MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in
MME programing. Published studies show that
melanoma EVs can educate
MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous
cancer cells within the
MME that alter the course of
metastasis has not been investigated at the mechanistic level. In this study,
melanoma parental cells (MPCs) and paired derivative cancer stem cell line
melanoma stem cells (MSCs) that were derived from
melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for
melanoma metastasis. We characterized miR-592, a relatively novel
microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target
protein tyrosine phosphatase non-receptor type7 (PTPN7), a
phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis,
melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC
melanoma cells.