Tumoural Hypoxic Extracellular Vesicles Foster a Protective Microenvironment in Triple-Negative Breast Cancer

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) is highly metastatic and relies on its tumor microenvironment (TME).
• Extracellular vesicles from hypoxic TNBC (EVh) are known to promote invasion, but their broader TME functions are unclear.

Purpose of the Study:

• To investigate the role of EVh in modulating the TME.
• To characterize EVh interactions with various cellular components of the TME.

Main Methods:

• Utilized a novel in vitro multicellular circulating co-culture system.
• Co-cultured EVh with tumor cells, endothelial cells, fibroblasts, monocytes, and macrophages.

Main Results:

• EVh promoted monocyte differentiation into M2-like macrophages.
• EVh inhibited macrophage-mediated phagocytosis of tumor and endothelial cells.
• EVh protected cellular integrity, increased pro-tumoral/angiogenic signaling, and stimulated collagen synthesis.
• EVh showed potential to induce differentiation into cancer-associated fibroblasts.

Conclusions:

• EVh plays a critical role in protecting tumor cells and fostering a pro-tumoral TME.
• The multicellular circulating co-culture system effectively demonstrated EVh's TME-modulating functions.
• This model system has potential for studying other tumor-related processes like metastasis.