Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells

doi:doi:10.1038/sj.bjc.6605143

Abstract

Background:

Human colorectal cancer is caused by mutations and is thought to be maintained by a population of cancer stem cells. Further phenotypic changes occurring at the invasive edge suggest that colon cancer cells are also regulated by their microenvironment. Type I collagen, a promoter of the malignant phenotype in pancreatic carcinoma cells, is highly expressed at the invasive front of human colorectal cancer.

Methods:

This study investigates the role of type I collagen in specifying the colorectal cancer cell phenotype. The effect of type I collagen on morphology, localisation of cell–cell adhesion proteins, differentiation and stem cell-like characteristics was examined in a panel of human colorectal carcinoma cell lines.

Results:

Human colorectal carcinoma cells grown on type I collagen in serum-free medium show an epithelial–mesenchymal-like transition (EMT-like), assuming a more flattened less cohesive morphology. Type I collagen downregulates E-cadherin and -catenin at cell–cell junctions. Furthermore, type I collagen inhibits differentiation, increases clonogenicity and promotes expression of stem cell markers CD133 and Bmi1. Type I collagen effects were partially abrogated by a function-blocking antibody to 2 integrin.

Conclusion:

Together, these results indicate that type I collagen promotes expression of a stem cell-like phenotype in human colorectal cancer cells likely through 21 integrin.

Keywords:

colorectal cancer, cancer stem cell, integrin, epithelial–mesenchymal transition, collagen, CD49b

Molecular Diagnostics