Effect of Tissue Factor on Colorectal Cancer Stem Cells

Anticancer Res. 2018 May;38(5):2635-2642. doi: 10.21873/anticanres.12505.

Abstract

Background/aim: Tissue factor (TF) expression increases cancer stem cell (CSC) activity in breast and lung cancer. There are ongoing studies focused on targeting CSCs via anti-TF treatment, for breast and lung cancer therapy. Herein, the aim was to determine whether targeting TF could have an anti-CSC therapeutic role in colorectal cancer (CRC).

Materials and methods: Evaluation of colonosphere-forming efficiency (CFE) and aldehyde dehydrogenase (ALDH) expression level was used to quantify CSC activity in two CRC cell lines, after TF knockdown (TFKD) or TF over-expression (TFOE).

Results: TFKD resulted in increased levels of ALDH in SW620 (1.31±0.04-fold, p<0.001) and DLD-1 (1.63±0.14-fold, p=0.04) cells. CFE was increased in SW620 (1.21±0.23% vs. 2.03±0.29%, p=0.01) and DLD-1 (0.41±0.12% vs. 0.68±0.9%, p=0.01) cells. Conversely, TFOE decreased ALDH expression (0.72±0.04-fold, p=0.001) and CFE (0.33±0.05% vs. 0.66±0.14%, p=0.006) in DLD-1, but had no impact on SW620 cells.

Conclusion: In the examined CRC cell lines, TF expression was inversely related to CSC activity suggesting that anti-TF therapies may not have a role in CRC treatment.

Keywords: Colorectal cancer; cancer stem cells; tissue factor.

MeSH terms

  • Aldehyde Dehydrogenase / analysis
  • Biomarkers, Tumor
  • Cell Division
  • Cell Line, Tumor
  • Colorectal Neoplasms / pathology*
  • Gene Knockdown Techniques
  • Genetic Vectors / pharmacology
  • Humans
  • Lentivirus / genetics
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / metabolism
  • Spheroids, Cellular
  • Thromboplastin / antagonists & inhibitors
  • Thromboplastin / genetics
  • Thromboplastin / physiology*

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Recombinant Proteins
  • Thromboplastin
  • Aldehyde Dehydrogenase