Caveolin-1-dependent tenascin C inclusion in extracellular vesicles is required to promote breast cancer cell malignancy

• Published in: Nanomedicine (London, England) England), 2023-10, Vol.18 (23), p.1651-1668
• Main Authors: Campos, America, Burgos-Ravanal, Renato, Lobos-González, Lorena, Huilcamán, Ricardo, González, María Fernanda, Díaz, Jorge, Verschae, Albano Cáceres, Acevedo, Juan Pablo, Carrasco, Macarena, Sepúlveda, Francisca, Jeldes, Emanuel, Varas-Godoy, Manuel, Leyton, Lisette, Quest, Andrew Fg
• Format: Article
• Language: English
• Subjects: Animals; breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; CAV1; Caveolin 1 - metabolism; Cell Line, Tumor; Disease Progression; exosomes; Extracellular Vesicles - metabolism; Humans; Medicin och hälsovetenskap; metastasis; Mice; Mice, SCID; Tenascin - metabolism; TNC
• ISSN: 1743-5889; 1748-6963; 1748-6963
• DOI: 10.2217/nnm-2023-0143

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. 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 assays. EVs were taken up by cells; however, only those containing TNC promoted invasiveness. , EVs lacking TNC ceased to promote tumor growth. CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer. 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.