Collagen mRNA levels changes during colorectal cancer carcinogenesis
1 Medical Department, Amager Hospital, Copenhagen S, Denmark
2 Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
3 Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
4 The Cancer Centre, Ulleval University Hospital, Oslo, Norway
5 Department of Pathology, Ulleval University Hospital, Oslo, Norway
6 Department of Environmental and Health Studies, Telemark University College, Bø, Norway
BMC Cancer 2009, 9:136 doi:10.1186/1471-2407-9-136Published: 7 May 2009
Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different α(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of type IV collagen (α1/α4/α6) and type VII collagen (α1) during colorectal cancer carcinogenesis.
Using quantitative RT-PCR, we have determined the mRNA levels for α1(IV), α4(IV), α6(IV), and α1(VII) in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to β-actin. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients.
The α1(IV) and α1(VII) mRNA levels were statistically significantly higher in colorectal cancer tissue (p < 0.001) as compared to corresponding tissue from healthy controls. This is an early event as tissue from adenomas also displayed a higher level. There were small changes in the levels of α4(IV). The level of α6(IV) was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p < 0.01). The localisation of type IV and type VII collagen was visualized by immunohistochemical staining.
Our results suggest that the down-regulation of α6(IV) mRNA coincides with the acquisition of invasive growth properties, whereas α1(IV) and α1(VII) mRNAs were up-regulated already in dysplastic tissue. There are no differences in collagen expression between tissues from healthy individuals and normal tissues from affected individuals.