Aspirin Affects MDA-MB-231 Vesicle Production and Their Capacity to Induce Fibroblasts towards a Pro-Invasive State

Area of Science:

• Oncology
• Cell Biology
• Pharmacology

Background:

• Long-term aspirin (acetylsalicylic acid) use is linked to reduced cancer incidence, but mechanisms remain unclear.
• Cancer-associated fibroblasts (CAFs) drive tumor progression, often activated by cancer cell-derived extracellular vesicles (EVs).
• Targeting tumor microenvironment (TME) communication is a strategy to control cancer progression.

Purpose of the Study:

• To investigate aspirin's effect on breast cancer cells, focusing on EV secretion.
• To determine how aspirin-modified EVs influence CAF biological properties.
• To assess aspirin's impact on cancer cell invasion mediated by CAFs.

Main Methods:

• Treatment of MDA-MB-231 breast cancer cells with aspirin (ASA).
• Analysis of EV production (quantity and size distribution) from treated and untreated cells.
• Stimulation of fibroblasts with ASA-treated EVs (EV-ASA) or control EVs (EV-CTR).
• Assessment of CAF markers (α-SMA, MMP2, FAP) and invasion assays using 3D fibroblast spheroids.

Main Results:

• Aspirin reduced the quantity and altered the size distribution of EVs from MDA-MB-231 cells.
• EV-ASA exposure led to lower α-SMA and MMP2 expression in fibroblasts compared to EV-CTR.
• Reduced breast cancer cell invasion was observed towards fibroblast spheroids pretreated with EV-ASA.

Conclusions:

• Aspirin interferes with tumor cell communication by modulating EV secretion.
• Aspirin-treated EVs have a diminished capacity to activate fibroblasts into CAFs.
• Aspirin may inhibit cancer progression by disrupting EV-mediated communication and CAF activation.