Alexandra Sneider, Ying Liu, Bartholomew Starich, Wenxuan Du, Praful R Nair, Carolyn Marar, Najwa Faqih, Gabrielle E Ciotti, Joo Ho Kim, Sejal Krishnan, Salma Ibrahim, Muna Igboko, Alexus Locke, Daniel M Lewis, Hanna Hong, Michelle N Karl, Raghav Vij, Gabriella C Russo, Estibaliz Gómez-de-Mariscal, Mehran Habibi, Arrate Muñoz-Barrutia, Luo Gu, T S Karin Eisinger-Mathason, Denis Wirtz
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 physiological matrix stiffness affects the quantity and protein cargo of small EVs produced by cancer cells, which in turn aid cancer cell dissemination. Primary patient breast tissue produces significantly more EVs from stiff tumor tissue than soft tumor adjacent tissue. EVs 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 to EVs from softer normal tissue (0...
April 17, 2024: Cancer Res Commun