Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo. Issue 13 (13th February 2023)

• Record Type: Journal Article
• Authors: Magoling, Bryan John Abel; Wu, Anthony Yan‐Tang; Chen, Yen‐Ju; Wong, Wendy Wan‐Ting; Chuo, Steven Ting‐Yu; Huang, Hsi‐Chien; Sung, Yun‐Chieh; Hsieh, Hsin Tzu; Huang, Poya; Lee, Kang‐Zhang; Huang, Kuan‐Wei; Chen, Ruey‐Hwa; Chen, Yunching; Lai, Charles Pin‐Kuang
• Is Part Of: Advanced materials. Volume 35:Issue 13(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-13
• Subjects: biodistribution -- breast cancer -- exosomes -- extracellular vesicles -- microvesicles -- organotropism; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202208966
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: 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. Abstract : Big and small extracellular vesicles circulate differentially and confer tumorigenic function modulatable by extracellular vesicle (EV) membrane proteins. Malignant breast cancers release more big EVs, in addition to small EVs, than normal cells to target organs and individually promote tumor growth via tumor‐progression‐associated EV surface membrane proteins.