Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells.
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 beta-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 alpha2 integrin.


CONCLUSIONS
Together, these results indicate that type I collagen promotes expression of a stem cell-like phenotype in human colorectal cancer cells likely through alpha2beta1 integrin.
Kirkland
S C
SC
Department of Histopathology, Imperial College London, DuCane Road, London W12 ONN, UK. s.kirkland@imperial.ac.uk
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D038982:Integrin alpha2beta1 / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; C069077:BMI1 protein, human; D024042:Collagen Type I; D006023:Glycoproteins; D038982:Integrin alpha2beta1; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1