Small Extracellular Vesicles Promote Stiffness-mediated Metastasis.
Cancer Res Commun
; 4(5): 1240-1252, 2024 May 09.
Article
en En
| MEDLINE
| ID: mdl-38630893
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 (ITGα2ß1, ITGα6ß4, ITGα6ß1, 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. SIGNIFICANCE:
Here we show that the quantity, cargo, and function of breast cancer-derived EVs vary with mechanical properties of the extracellular microenvironment.
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MEDLINE
Asunto principal:
Pez Cebra
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Neoplasias de la Mama
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Microambiente Tumoral
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Vesículas Extracelulares
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res Commun
Año:
2024
Tipo del documento:
Article