{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sneider A"],"funding":["HHS | National Institutes of Health","Ministerio de Ciencia, Innovación y Universidades","NIA NIH HHS","HHS | NIH | National Cancer Institute","HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","NSF | National Science Foundation Graduate Research Fellowship Program","NCI NIH HHS","HHS | NIH | National Institute on Aging","NIAMS NIH HHS"],"pagination":["1240-1252"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11080964"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(5)"],"pubmed_abstract":["Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiologic matrix stiffness affects the quantity and protein cargo of small extracellular vesicles (EV) produced by cancer cells, which in turn aid cancer cell dissemination. Primary patient breast tissue released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2β1, ITGα6β4, ITGα6β1, CD44) compared with EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix proteins including collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer-associated fibroblast phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment.<h4>Significance</h4>Here we show that the quantity, cargo, and function of breast cancer-derived EVs vary with mechanical properties of the extracellular microenvironment."],"journal":["Cancer research communications"],"pubmed_title":["Small Extracellular Vesicles Promote Stiffness-mediated Metastasis."],"pmcid":["PMC11080964"],"funding_grant_id":["U01AG060903","U54 AR081774","U54CA210173","U54 CA210173","1746891","R01 CA174388","U54 CA268083","R01CA174388","U54 CA143868","U54AR081774","U54CA268083","TEC2015-73064-EXP","U01 AG060903","PID2019-109820RB-I00","U54CA143868","TEC201678052-R"],"pubmed_authors":["Faqih N","Karl MN","Ciotti GE","Hong H","Vij R","Eisinger-Mathason TSK","Du W","Marar C","Starich B","Wirtz D","Nair PR","Krishnan S","Russo GC","Liu Y","Locke A","Habibi M","Sneider A","Munoz-Barrutia A","Gu L","Ibrahim S","Kim JH","Lewis DM","Gomez-de-Mariscal E","Igboko M"],"additional_accession":[]},"is_claimable":false,"name":"Small Extracellular Vesicles Promote Stiffness-mediated Metastasis.","description":"Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiologic matrix stiffness affects the quantity and protein cargo of small extracellular vesicles (EV) produced by cancer cells, which in turn aid cancer cell dissemination. Primary patient breast tissue released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2β1, ITGα6β4, ITGα6β1, CD44) compared with EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix proteins including collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer-associated fibroblast phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment.<h4>Significance</h4>Here we show that the quantity, cargo, and function of breast cancer-derived EVs vary with mechanical properties of the extracellular microenvironment.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T18:58:01.096Z","creation":"2026-05-19T03:07:31.325Z"},"accession":"S-EPMC11080964","cross_references":{"pubmed":["38630893"],"doi":["10.1158/2767-9764.CRC-23-0431"]}}