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

M R Loebinger1, E K Sage, D Davies

  • 1Centre For Respiratory Research, Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, UK.

British Journal of Cancer
|November 11, 2010
PubMed
Abstract

Insights

Engineered mesenchymal stem cells (MSCs) expressing TNF-related apoptosis-inducing ligand (TRAIL) effectively target and eliminate cancer stem cells (CSCs). This approach shows promise in preventing cancer relapse when combined with chemotherapy.

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.

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