PMID- 37929694 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20240422 IS - 1748-6963 (Electronic) IS - 1743-5889 (Linking) VI - 18 IP - 23 DP - 2023 Oct TI - Caveolin-1-dependent tenascin C inclusion in extracellular vesicles is required to promote breast cancer cell malignancy. PG - 1651-1668 LID - 10.2217/nnm-2023-0143 [doi] AB - Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer. FAU - Campos, America AU - Campos A AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Cientifico y Tecnologico de Excelencia Ciencia y Vida, Santiago, 8340148, Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. AD - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, Scotland. FAU - Burgos-Ravanal, Renato AU - Burgos-Ravanal R AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. FAU - Lobos-Gonzalez, Lorena AU - Lobos-Gonzalez L AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. AD - Centro de Medicina Regenerativa, Facultad de Medicina-Clinica Alemana, Universidad del Desarrollo, Santiago, 7610615, Chile. FAU - Huilcaman, Ricardo AU - Huilcaman R AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. FAU - Gonzalez, Maria Fernanda AU - Gonzalez MF AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. FAU - Diaz, Jorge AU - Diaz J AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. FAU - Verschae, Albano Caceres AU - Verschae AC AD - Laboratorio de Biologia Celular del Cancer, CEBICEM, Universidad San Sebastian, Santiago, 7510157, Chile. AD - Department of Oncology/Pathology, Karolinska Institutet, Stockholm, 17177, Sweden. FAU - Acevedo, Juan Pablo AU - Acevedo JP AD - Center of Interventional Medicine for Precision & Advanced Cellular Therapy (IMPACT), Santiago, 8331150, Chile. FAU - Carrasco, Macarena AU - Carrasco M AD - Centro Cientifico y Tecnologico de Excelencia Ciencia y Vida, Santiago, 8340148, Chile. FAU - Sepulveda, Francisca AU - Sepulveda F AD - Centro Cientifico y Tecnologico de Excelencia Ciencia y Vida, Santiago, 8340148, Chile. AD - Centro de Medicina Regenerativa, Facultad de Medicina-Clinica Alemana, Universidad del Desarrollo, Santiago, 7610615, Chile. FAU - Jeldes, Emanuel AU - Jeldes E AD - Centro Cientifico y Tecnologico de Excelencia Ciencia y Vida, Santiago, 8340148, Chile. AD - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, Scotland. FAU - Varas-Godoy, Manuel AU - Varas-Godoy M AD - Centro Cientifico y Tecnologico de Excelencia Ciencia y Vida, Santiago, 8340148, Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. AD - Laboratorio de Biologia Celular del Cancer, CEBICEM, Universidad San Sebastian, Santiago, 7510157, Chile. FAU - Leyton, Lisette AU - Leyton L AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. FAU - Quest, Andrew Fg AU - Quest AF AUID- ORCID: 0000-0001-8755-1590 AD - Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cancer (CEMC), Programa de Biologia Celular y Molecular, Facultad de Medicina, 8380492, Universidad de Chile. AD - Centro Avanzado para Estudios en Enfermedades Cronicas (ACCDIS), Santiago, 8380492, Chile. LA - eng GR - 21130102, 21161246, 21170292, 21200147/ANID PhD fellowship/ GR - 1190928, 1200836, 1210644, 1211223/Fondo Nacional de Desarrollo Cientifico y Tecnologico/ GR - 15130011/Fondo de Financiamiento de Centros de Investigacion en Areas Prioritarias/ GR - FB210008, FB210024/ANID BASAL/ GR - 3170169/ANID postdoctoral/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231106 PL - England TA - Nanomedicine (Lond) JT - Nanomedicine (London, England) JID - 101278111 RN - 0 (CAV1 protein, human) RN - 0 (Caveolin 1) RN - 0 (TNC protein, human) RN - 0 (Tenascin) SB - IM MH - Humans MH - Cell Line, Tumor MH - *Breast Neoplasms/metabolism/pathology MH - *Caveolin 1/metabolism MH - *Extracellular Vesicles/metabolism MH - *Tenascin/metabolism MH - Animals MH - Mice MH - Mice, SCID MH - Disease Progression OAB - Caveolin-1 (CAV1) is a protein that in breast cancer increases with disease progression. Extracellular vesicles (EVs) from breast cancer cells with CAV1 also contain Tenascin C (TNC) protein, but the importance of TNC remained to be defined. EVs were identified by size, microscopy and protein analysis. The effects of EVs on breast cancer cells were studied using cells and experiments in animals. CAV1 expression promotes TNC inclusion into EVs, which increased the aggressiveness of recipient breast cancer cells. In animals, only EVs with TNC increased features associated with cancer spread, while EVs lacking TNC reduced tumor growth. OABL- eng OTO - NOTNLM OT - CAV1 OT - TNC OT - breast cancer OT - exosomes OT - metastasis EDAT- 2023/11/06 06:42 MHDA- 2023/11/06 06:43 CRDT- 2023/11/06 05:52 PHST- 2023/11/06 06:43 [medline] PHST- 2023/11/06 06:42 [pubmed] PHST- 2023/11/06 05:52 [entrez] AID - 10.2217/nnm-2023-0143 [doi] PST - ppublish SO - Nanomedicine (Lond). 2023 Oct;18(23):1651-1668. doi: 10.2217/nnm-2023-0143. Epub 2023 Nov 6.