TRAIL-expressing mesenchymal stem cells kill the putative cancer stem cell population

Area of Science:

• Oncology
• Cancer Stem Cell Biology
• Regenerative Medicine

Background:

• Tumors harbor stem-like side population (SP) cells with high tumorigenic potential.
• SP cells exhibit resistance to conventional therapies, contributing to treatment failure and relapse.
• Identifying and targeting SP cells is crucial for effective cancer treatment.

Purpose of the Study:

• To investigate the efficacy of TNF-related apoptosis-inducing ligand (TRAIL)-engineered mesenchymal stem cells (MSCs) against cancer stem cells (CSCs).
• To evaluate the synergistic effects of TRAIL-expressing MSCs and chemotherapy on SP cancer cells.
• To explore the potential of this approach in preventing cancer recurrence.

Main Methods:

• Mesenchymal stem cells (MSCs) were genetically modified to express TRAIL.
• Squamous (H357) and lung (A549) cancer cell lines were separated into side population (SP) and non-side population (non-SP) fractions using Hoechst flow cytometry.
• The impact of TRAIL-expressing MSCs and mitoxantrone chemotherapy on SP and non-SP cancer cell survival, growth, and colony-forming ability was assessed.

Main Results:

• TRAIL-expressing MSCs demonstrated migration to tumor sites and inhibited primary tumor and metastasis growth.
• These engineered MSCs induced apoptosis and reduced colony formation in SP cells from squamous and lung cancer lines.
• A synergistic effect was observed when TRAIL-expressing MSCs were combined with chemotherapy for apoptosis induction in SP cells.

Conclusions:

• Cancer stem cells (SP cells) are sensitive to TRAIL-expressing MSCs.
• TRAIL-expressing MSCs hold potential for preventing cancer relapse.
• Targeting cancer stem cells with engineered MSCs represents a promising therapeutic strategy.