Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs)

Area of Science:

• Oncology
• Cell Biology
• Biomedical Engineering

Background:

• Breast cancer relapse often stems from drug-resistant dormant tumor cells.
• Mesenchymal stem/stromal cells (MSCs) influence tumor stroma and cancer cell behavior.
• Understanding tumor dormancy is crucial for preventing cancer recurrence.

Purpose of the Study:

• To investigate the impact of MSCs on breast cancer cell (BCC) dormancy.
• To elucidate the mechanism by which MSCs affect BCC survival and dormancy.
• To establish a 3D coculture model for studying tumor-stromal interactions.

Main Methods:

• Utilized 3D cocultures to simulate tumor niche interactions between MSCs and BCCs.
• Observed MSCs surrounding, promoting spheroid formation, and being internalized by BCCs (cannibalism).
• Analyzed transcriptome profiles of BCCs after MSC cannibalism and assessed survival and tumorigenicity.

Main Results:

• MSCs were sequentially internalized and degraded by BCCs, a process resembling cell cannibalism.
• MSC cannibalism enhanced BCC survival under nutrient deprivation but suppressed tumorigenicity, indicating dormancy.
• BCCs acquired a unique molecular signature associated with prosurvival factors, tumor suppressors, and senescence-associated secretory phenotype.

Conclusions:

• Breast cancer cells under duress may enter dormancy by cannibalizing MSCs.
• This process offers a novel therapeutic avenue for preventing cancer recurrence.
• The 3D coculture model serves as a valuable tool for further research into MSC antitumor activity and cell cannibalism.