Hepatic Stellate Cells Activated by Cancer Cell-derived AMIGO2-containing Small Extracellular Vesicles Promote Cancer...

Area of Science:

• Oncology
• Cell Biology
• Extracellular Vesicles

Background:

• Amphoterin-induced gene and open reading frame 2 (AMIGO2) drives liver metastasis by regulating cancer cell adhesion.
• AMIGO2-containing small extracellular vesicles (sEVs) from gastric cancer (GC) cells promote pre-metastatic niche formation.
• The role of AMIGO2-sEVs in promoting cancer cell invasion into the liver parenchyma was previously unclear.

Purpose of the Study:

• To investigate if AMIGO2-containing sEVs activate hepatic stellate cells (HSCs).
• To determine if activated HSCs promote GC cell migration into the liver.
• To elucidate the mechanism by which AMIGO2-sEVs influence liver metastasis.

Main Methods:

• Established AMIGO2-over-expressing and control GC cell lines (MKN28).
• Treated human HSCs with sEVs and analyzed supernatant for effects on GC cell migration and NF-kB translocation.
• Utilized a chemokine array to identify secreted factors influenced by sEV treatment.

Main Results:

• AMIGO2-containing sEVs activated HSCs, leading to increased IL-8 secretion via NF-kB nuclear translocation.
• The IL-8-rich supernatant significantly enhanced GC cell migration.
• Neutralization of IL-8 abolished the pro-migratory effect on GC cells.

Conclusions:

• AMIGO2-sEVs activate HSCs and induce IL-8 secretion, promoting GC cell migration into the liver parenchyma.
• This mechanism contributes to pre-metastatic niche formation in the liver.
• AMIGO2-containing sEVs represent a potential therapeutic target for preventing liver metastasis.