Consecutive entosis stages in human substrate-dependent cultured cells

Area of Science:

• Cell Biology
• Cancer Research
• Cytopathology

Background:

• Entosis, or cell-in-cell death, is a known phenomenon in tumor epithelial cells.
• While studied in suspension cultures, entosis in substrate-dependent cells is poorly understood.

Purpose of the Study:

• To elucidate the kinetics and mechanisms of entosis in human substrate-dependent tumor cell lines.
• To identify the cellular components essential for entosis in these specific cell types.

Main Methods:

• Utilized electron, confocal, and time-lapse microscopy.
• Employed pharmacological inhibition of intracellular components.
• Examined two human substrate-dependent tumor cell lines (A431 and MCF7).

Main Results:

• Identified and characterized five distinct, sequential stages of entosis common to both cell lines.
• Demonstrated the critical roles of actin filaments, microtubules, and the Golgi apparatus in the invasion phase of entosis.
• Confirmed the involvement of lysosomal activation in the degradation of the internalized cell.
• Observed the formation of desmosomes between invading and entotic cells.

Conclusions:

• Entosis in substrate-dependent tumor cells proceeds through a defined series of stages.
• Actin, microtubules, and Golgi are vital for the invasion step of entosis.
• Internalized cell degradation relies on lysosomal pathways, independent of Golgi integrity.