Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes
Exosomes are small extracellular vesicles critical for intercellular signaling via their delivery of cargoes, including proteins, DNA, RNA, lipids, and metabolites. Exosomes play essential roles in remodeling the tumor microenvironment (TME) for tumor growth, metastasis, and drug resistance. Aminate...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.779939/full |
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| author | Jiawei Huo Jiawei Huo Wei Zhou Yang Liu Yang Liu Sifen Yang Jie Li Chunru Wang Chunru Wang |
| author_facet | Jiawei Huo Jiawei Huo Wei Zhou Yang Liu Yang Liu Sifen Yang Jie Li Chunru Wang Chunru Wang |
| author_sort | Jiawei Huo |
| collection | DOAJ |
| description | Exosomes are small extracellular vesicles critical for intercellular signaling via their delivery of cargoes, including proteins, DNA, RNA, lipids, and metabolites. Exosomes play essential roles in remodeling the tumor microenvironment (TME) for tumor growth, metastasis, and drug resistance. Aminated fullerenes (e.g., C70-ethylenediamine [EDA]) exhibit antineoplastic effects by targeting multiple functional proteins. Nanosized C70-EDA with positive surface charges tends to be taken up by monocytes in the bloodstream and monocyte-derived macrophages in the TME. Herein, the alterations of monocytes and monocyte-derived exosomes by C70-EDA have been investigated. C70-EDA reprogramed THP-1 monocyte to an M2-like state and substantially increased the protein content in exosomes secreted by M2-like monocytes. Notably, C70-EDA-induced M2-like monocytes released exosomes that triggered the proliferation of recipient tumor cells, which may alleviate the antineoplastic efficacy of C70-EDA. As revealed by proteomic profiling of exosomes, this outcome is probably a result of Rho GTPase/p21-activated kinase (PAK) pathway activation in recipient tumor cells induced by upregulated exosomal proteins. This work indicates a promising strategy in which aminated fullerenes can be combined with PAK inhibitors for cancer therapy. |
| first_indexed | 2024-04-13T15:55:40Z |
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| id | doaj.art-cc74aec07cfd452c9682e2520f3d9a4d |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T15:55:40Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-cc74aec07cfd452c9682e2520f3d9a4d2022-12-22T02:40:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-03-011210.3389/fonc.2022.779939779939Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived ExosomesJiawei Huo0Jiawei Huo1Wei Zhou2Yang Liu3Yang Liu4Sifen Yang5Jie Li6Chunru Wang7Chunru Wang8Beijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaBeijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing, ChinaBeijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaBeijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing, ChinaBeijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing, ChinaBeijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaExosomes are small extracellular vesicles critical for intercellular signaling via their delivery of cargoes, including proteins, DNA, RNA, lipids, and metabolites. Exosomes play essential roles in remodeling the tumor microenvironment (TME) for tumor growth, metastasis, and drug resistance. Aminated fullerenes (e.g., C70-ethylenediamine [EDA]) exhibit antineoplastic effects by targeting multiple functional proteins. Nanosized C70-EDA with positive surface charges tends to be taken up by monocytes in the bloodstream and monocyte-derived macrophages in the TME. Herein, the alterations of monocytes and monocyte-derived exosomes by C70-EDA have been investigated. C70-EDA reprogramed THP-1 monocyte to an M2-like state and substantially increased the protein content in exosomes secreted by M2-like monocytes. Notably, C70-EDA-induced M2-like monocytes released exosomes that triggered the proliferation of recipient tumor cells, which may alleviate the antineoplastic efficacy of C70-EDA. As revealed by proteomic profiling of exosomes, this outcome is probably a result of Rho GTPase/p21-activated kinase (PAK) pathway activation in recipient tumor cells induced by upregulated exosomal proteins. This work indicates a promising strategy in which aminated fullerenes can be combined with PAK inhibitors for cancer therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.779939/fullC70-EDAM2-like monocyte-derived exosomeproteomicsRho GTPase/PAK signalingtumor proliferation |
| spellingShingle | Jiawei Huo Jiawei Huo Wei Zhou Yang Liu Yang Liu Sifen Yang Jie Li Chunru Wang Chunru Wang Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes Frontiers in Oncology C70-EDA M2-like monocyte-derived exosome proteomics Rho GTPase/PAK signaling tumor proliferation |
| title | Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes |
| title_full | Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes |
| title_fullStr | Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes |
| title_full_unstemmed | Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes |
| title_short | Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes |
| title_sort | potential resistance to antineoplastic aminated fullerenes mediated by m2 like monocyte derived exosomes |
| topic | C70-EDA M2-like monocyte-derived exosome proteomics Rho GTPase/PAK signaling tumor proliferation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.779939/full |
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