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000290080 1001_ $$00000-0001-5425-4901$$aParikh, Roma$$b0
000290080 245__ $$aRecycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.
000290080 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2024
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000290080 520__ $$aExtracellular 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 'second-hand' 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.
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000290080 650_7 $$2Other$$aAngiogenesis
000290080 650_7 $$2Other$$aCell-to-Cell-Transfer
000290080 650_7 $$2Other$$aHeterogeneity
000290080 650_7 $$2Other$$aMelanosomes
000290080 650_7 $$2Other$$aTumor Associated Macrophages
000290080 7001_ $$00000-0001-6364-9307$$aParikh, Shivang$$b1
000290080 7001_ $$aBerzin, Daniella$$b2
000290080 7001_ $$aVaknine, Hananya$$b3
000290080 7001_ $$00000-0002-0307-7631$$aOvadia, Shai$$b4
000290080 7001_ $$aLikonen, Daniela$$b5
000290080 7001_ $$00000-0001-8308-2790$$aGreenberger, Shoshana$$b6
000290080 7001_ $$00000-0001-9160-7411$$aScope, Alon$$b7
000290080 7001_ $$aElgavish, Sharona$$b8
000290080 7001_ $$aNevo, Yuval$$b9
000290080 7001_ $$aPlaschkes, Inbar$$b10
000290080 7001_ $$aNizri, Eran$$b11
000290080 7001_ $$00000-0001-9914-3770$$aKobiler, Oren$$b12
000290080 7001_ $$aMaliah, Avishai$$b13
000290080 7001_ $$0P:(DE-HGF)0$$aZaremba, Laureen$$b14
000290080 7001_ $$00000-0002-0008-5513$$aMohan, Vishnu$$b15
000290080 7001_ $$aSagi, Irit$$b16
000290080 7001_ $$aAshery-Padan, Ruth$$b17
000290080 7001_ $$aCarmi, Yaron$$b18
000290080 7001_ $$00000-0002-7801-3499$$aLuxenburg, Chen$$b19
000290080 7001_ $$0P:(DE-He78)c684a26e52cc44716354a4d15f530b4e$$aHoheisel, Jörg$$b20$$udkfz
000290080 7001_ $$aKhaled, Mehdi$$b21
000290080 7001_ $$00000-0001-5902-9420$$aLevesque, Mitchell P$$b22
000290080 7001_ $$00000-0003-2683-8779$$aLevy, Carmit$$b23
000290080 773__ $$0PERI:(DE-600)1467419-1$$a10.1038/s44318-024-00103-7$$n17$$p3553-3586$$tThe EMBO journal$$v43$$x0261-4189$$y2024
000290080 8564_ $$uhttps://inrepo02.dkfz.de/record/290080/files/parikh-et-al-recycled-melanoma-secreted-melanosomes-regulate-tumor-associated-macrophage-diversification.pdf
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