In Situ Investigation of Intercellular Communication in Ferroptosis Integrated Scanning Electrochemical Microscopy...

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Immunology

Background:

• Ferroptosis, a regulated form of cell death, is a promising cancer treatment strategy.
• Tumor-associated macrophages (TAMs) significantly influence cancer progression within the tumor microenvironment.
• Understanding cancer cell-macrophage communication is crucial for developing effective cancer therapies.

Purpose of the Study:

• To investigate the role of TAMs in regulating ferroptosis of triple-negative breast cancer (TNBC) cells.
• To elucidate the underlying intercellular communication mechanisms between TNBC cells and TAMs during ferroptosis.
• To explore targeting TAMs as a therapeutic strategy for TNBC.

Main Methods:

• Development of a microfluidic device for on-chip co-culture of TNBC cells and TAMs.
• Utilizing scanning electrochemical microscopy (SECM) for in situ monitoring of ferroptosis-related parameters (ROS, GSH, cell membrane permeability).
• Investigating the STAT3 signaling pathway in TAM-mediated ferroptosis suppression.

Main Results:

• TAMs were found to suppress ferroptosis in TNBC cells by partially restoring glutathione (GSH) efflux and impairing reactive oxygen species (ROS) production and cell membrane integrity.
• TNBC cells promoted M2 polarization of macrophages.
• M2-TAMs suppressed TNBC ferroptosis via the STAT3 signaling pathway, which was confirmed by observing increased ROS and membrane permeability and decreased GSH efflux upon STAT3 inhibition.

Conclusions:

• TAMs play a suppressive role in TNBC ferroptosis through M2 polarization and STAT3 signaling.
• Targeting the STAT3 pathway in TAMs can enhance ferroptosis in TNBC.
• This study highlights a potential therapeutic strategy for TNBC by modulating TAMs to promote ferroptosis.