Aged breast matrix bound vesicles promote breast cancer invasiveness

Area of Science:

• Biomedical Science
• Cell Biology
• Cancer Research

Background:

• Aging is a significant risk factor for breast cancer.
• While cellular aging's impact is studied, the aging breast tissue microenvironment, particularly the extracellular matrix (ECM), remains under-explored.
• Matrix-bound vesicles (MBVs) are newly identified components within the breast ECM with potential regulatory roles.

Purpose of the Study:

• To identify and characterize matrix-bound vesicles (MBVs) in young versus aged healthy mouse breast tissue.
• To investigate the effect of MBVs from different age groups on normal and cancerous human mammary epithelial cells.
• To elucidate the role of MBVs in age-related breast cancer progression and metastasis.

Main Methods:

• Identification and characterization of MBVs in young and aged mouse breast tissue.
• Vesicle labeling technology to visualize cellular uptake of MBVs from decellularized tissue.
• miRNA and cytokine profiling of MBVs.
• Cell culture experiments using normal (KTB21) and cancerous (MDA-MB-231) mammary cells treated with MBVs or specific enriched factors.

Main Results:

• MBVs were identified in healthy mouse breast ECM and shown to be internalized by mammary cells.
• MBVs isolated from aged mice exhibited a shift towards a more tumorigenic and invasive phenotype.
• Aged MBVs showed increased cancer-associated cytokines and oncomiRs (miR-10b, miR-30e, miR-210) compared to young MBVs.
• Treatment with aged MBVs or their enriched miRNAs/AdipoRon agonist significantly increased cell motility and invasion.

Conclusions:

• MBVs play a regulatory role in the tissue microenvironment.
• The composition of MBVs changes with age, promoting a pro-tumorigenic environment.
• Understanding MBV function and cargo is crucial for comprehending breast cancer progression and metastasis in aging populations.