@article {Parikh2024-yn,
	title = {Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification},
	journal = {EMBO J.},
	year = {2024},
	publisher = {Springer Science and Business Media LLC},
	abstract = {Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as {\textquoteleft}{\textquoteleft}second-hand{\textquoteright}{\textquoteright} EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.},
	keywords = {Angiogenesis, Cell-to-Cell-Transfer, Heterogeneity, Melanosomes, Tumor Associated Macrophages},
	author = {Parikh, Roma and Parikh, Shivang and Berzin, Daniella and Vaknine, Hananya and Ovadia, Shai and Likonen, Daniela and Greenberger, Shoshana and Scope, Alon and Elgavish, Sharona and Nevo, Yuval and Plaschkes, Inbar and Nizri, Eran and Kobiler, Oren and Maliah, Avishai and Zaremba, Laureen and Mohan, Vishnu and Sagi, Irit and Ashery-Padan, Ruth and Carmi, Yaron and Luxenburg, Chen and Hoheisel, J{\"o}rg D and Khaled, Mehdi and Levesque, Mitchell P and Levy, Carmit}
}
