Cancer-Derived Extracellular Vesicle ITGB2 Promotes the Progression of Triple-Negative Breast Cancer via the Activation of Cancer-Associated Fibroblasts

IF 4.4 4区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Global Challenges Pub Date : 2025-01-23 DOI:10.1002/gch2.202400235

Jingjing Fan, Tong Sha, Binlin Ma

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Abstract

Breast cancer is the most prevalent cancer and a leading cause of death among women globally, posing a significant public health challenge. Triple-negative breast cancer (TNBC), an aggressive subtype accounting for 15–20% of all breast cancers, lacks targeted therapies due to the absence of hormone receptors and HER2, resulting in poor prognosis and high recurrence rates. This study investigates the role of cancer-derived extracellular vesicle (EV) integrin beta-2 (ITGB2) in TNBC progression. These findings reveal that ITGB2 is significantly overexpressed in TNBC tissues and serum EVs, correlating with advanced tumor stages and poor patient survival. ITGB2 enhances TNBC progression by activating cancer-associated fibroblasts (CAFs) within the tumor microenvironment, promoting tumor growth, migration, and invasion. Mechanistic studies demonstrate that EV ITGB2 facilitates CAF activation, driving tumor-stroma interactions that support TNBC progression. These results highlight ITGB2 as a potential biomarker and therapeutic target in TNBC, emphasizing the need for novel interventions to combat this challenging breast cancer subtype.

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