Exosomes in Human Breast Milk Promote EMT

Area of Science:

• Cell biology
• Oncology
• Reproductive biology

Background:

• Pregnancy elevates breast cancer risk for up to five years postpartum.
• The breast microenvironment during weaning and involution supports tumor growth.
• Exosomes mediate cell-cell communication in lactation and breast cancer.

Purpose of the Study:

• To investigate if molecules within milk exosomes from healthy lactating women influence breast cancer development and progression.
• To determine the role of exosome content in modulating breast cancer cell behavior.

Main Methods:

• Collected milk exosomes from 13 nursing women at transitional, mature, and wean stages.
• Measured expression of six breast cancer-associated proteins in exosomes.
• Assessed the impact of high TGFβ2-containing exosomes on breast cell epithelial-mesenchymal transition (EMT) markers.

Main Results:

• Human milk exosomes were internalized by both benign and malignant breast cells.
• TGFβ2 levels were significantly elevated in exosomes during the wean stage (P = 0.01).
• High TGFβ2 exosomes induced EMT in breast cells, characterized by morphological changes, altered actin cytoskeleton, loss of cell-cell junctions, and changes in EMT markers (E-cadherin, α-SMA, vimentin).

Conclusions:

• TGFβ2 is significantly upregulated in breast milk exosomes during weaning and early involution.
• Breast milk exosomes with high TGFβ2 levels can induce changes in breast epithelial cells consistent with cancer development and progression.
• High TGFβ2-expressing breast milk exosomes may play a role in influencing breast cancer risk.