Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy

Area of Science:

• Oncology
• Biotechnology
• Cell Biology

Background:

• Cancer treatment faces challenges due to heterogeneous cell populations with varying drug responses.
• Drug-resistant cancer cell sub-populations are scarce, hindering the study of resistance mechanisms.

Purpose of the Study:

• To develop a label-free microfluidic technique for separating chemoresistant and chemosensitive cancer cells.
• To identify molecular mechanisms underlying cancer drug resistance.
• To validate the therapeutic potential of targeting identified resistance pathways.

Main Methods:

• Utilized a label-free microfluidic device to sort cancer cells based on differential cellular stiffness.
• Analyzed molecular distinctions between chemoresistant and chemosensitive cell sub-populations.
• Investigated mechanisms including apoptosis sensitivity, metabolic activity, drug extrusion, and estrogen receptor involvement.

Main Results:

• Successfully separated cancer cells into chemoresistant and chemosensitive populations.
• Identified key drug resistance mechanisms: reduced apoptosis sensitivity, increased metabolism, drug extrusion, and estrogen receptor activity in leukemia.
• Demonstrated a sevenfold increase in cytotoxicity by combining chemotherapy with inhibitors of identified resistance pathways.

Conclusions:

• Microfluidic sorting is effective for isolating cancer cell sub-populations based on drug resistance.
• This method facilitates the discovery of novel molecular mechanisms of drug resistance.
• Targeting identified resistance pathways significantly enhances the efficacy of cancer therapies.