Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2024
|
| Online Access: | https://hdl.handle.net/1721.1/154934 |
| _version_ | 1824458058465542144 |
|---|---|
| author | Parikh, Roma Parikh, Shivang Berzin, Daniella Vaknine, Hananya Ovadia, Shai Likonen, Daniela Greenberger, Shoshana Scope, Alon Elgavish, Sharona Nevo, Yuval Plaschkes, Inbar Nizri, Eran Kobiler, Oren Maliah, Avishai Zaremba, Laureen Mohan, Vishnu Sagi, Irit Ashery-Padan, Ruth Carmi, Yaron Luxenburg, Chen Hoheisel, Jörg D Khaled, Mehdi Levesque, Mitchell P Levy, Carmit |
| author2 | Ragon Institute of MGH, MIT and Harvard |
| author_facet | Ragon Institute of MGH, MIT and Harvard Parikh, Roma Parikh, Shivang Berzin, Daniella Vaknine, Hananya Ovadia, Shai Likonen, Daniela Greenberger, Shoshana Scope, Alon Elgavish, Sharona Nevo, Yuval Plaschkes, Inbar Nizri, Eran Kobiler, Oren Maliah, Avishai Zaremba, Laureen Mohan, Vishnu Sagi, Irit Ashery-Padan, Ruth Carmi, Yaron Luxenburg, Chen Hoheisel, Jörg D Khaled, Mehdi Levesque, Mitchell P Levy, Carmit |
| author_sort | Parikh, Roma |
| collection | MIT |
| description | 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 “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. |
| first_indexed | 2024-09-23T11:04:42Z |
| format | Article |
| id | mit-1721.1/154934 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:19:51Z |
| publishDate | 2024 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1549342025-02-04T02:04:52Z Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification Parikh, Roma Parikh, Shivang Berzin, Daniella Vaknine, Hananya Ovadia, Shai Likonen, Daniela Greenberger, Shoshana Scope, Alon Elgavish, Sharona Nevo, Yuval Plaschkes, Inbar Nizri, Eran Kobiler, Oren Maliah, Avishai Zaremba, Laureen Mohan, Vishnu Sagi, Irit Ashery-Padan, Ruth Carmi, Yaron Luxenburg, Chen Hoheisel, Jörg D Khaled, Mehdi Levesque, Mitchell P Levy, Carmit Ragon Institute of MGH, MIT and Harvard 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 “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. 2024-05-13T18:05:00Z 2024-05-13T18:05:00Z 2024-05-08 2024-05-12T03:12:03Z Article http://purl.org/eprint/type/JournalArticle 1460-2075 https://hdl.handle.net/1721.1/154934 Parikh, Roma, Parikh, Shivang, Berzin, Daniella, Vaknine, Hananya, Ovadia, Shai et al. 2024. "Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification." The EMBO Journal. en 10.1038/s44318-024-00103-7 The EMBO Journal Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Springer Science and Business Media LLC |
| spellingShingle | Parikh, Roma Parikh, Shivang Berzin, Daniella Vaknine, Hananya Ovadia, Shai Likonen, Daniela Greenberger, Shoshana Scope, Alon Elgavish, Sharona Nevo, Yuval Plaschkes, Inbar Nizri, Eran Kobiler, Oren Maliah, Avishai Zaremba, Laureen Mohan, Vishnu Sagi, Irit Ashery-Padan, Ruth Carmi, Yaron Luxenburg, Chen Hoheisel, Jörg D Khaled, Mehdi Levesque, Mitchell P Levy, Carmit Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification |
| title | Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification |
| title_full | Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification |
| title_fullStr | Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification |
| title_full_unstemmed | Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification |
| title_short | Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification |
| title_sort | recycled melanoma secreted melanosomes regulate tumor associated macrophage diversification |
| url | https://hdl.handle.net/1721.1/154934 |
| work_keys_str_mv | AT parikhroma recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT parikhshivang recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT berzindaniella recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT vakninehananya recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT ovadiashai recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT likonendaniela recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT greenbergershoshana recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT scopealon recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT elgavishsharona recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT nevoyuval recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT plaschkesinbar recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT nizrieran recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT kobileroren recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT maliahavishai recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT zarembalaureen recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT mohanvishnu recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT sagiirit recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT asherypadanruth recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT carmiyaron recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT luxenburgchen recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT hoheiseljorgd recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT khaledmehdi recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT levesquemitchellp recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification AT levycarmit recycledmelanomasecretedmelanosomesregulatetumorassociatedmacrophagediversification |