Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo
© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.
Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 13 vom: 07. März, Seite e2208966 |
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1. Verfasser: | |
Weitere Verfasser: | , , , , , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2023
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Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
Schlagworte: | Journal Article biodistribution breast cancer exosomes extracellular vesicles microvesicles organotropism Membrane Proteins |
Zusammenfassung: | © 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH. Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100-200 nm, exosomes) are intensely investigated, the properties and functions of medium and large EVs (big EVs (bEVs); >200 nm, microvesicles) are less well explored. Here, bEVs and sEVs are identified as distinct EV populations, and it is determined that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence-resonance-energy-transfer (BRET)-based EV reporter, reveals dose-dependent EV biodistribution at nonlethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, yet individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass-spectrometry-identified tumor-progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include solute carrier family 29 member 1, Cd9, and Cd44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications |
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Beschreibung: | Date Completed 30.03.2023 Date Revised 30.03.2023 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-4095 |
DOI: | 10.1002/adma.202208966 |