Collagen mRNA levels changes during colorectal cancer carcinogenesis

Abstract

BackgroundInvasive 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.MethodsUsing 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.ResultsThe 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.ConclusionOur 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.

Significance of Streptococcus gallolyticus subsp. gallolyticus Association With Colorectal Cancer

“…While collagen type I is the major structural component of human heart, collagen type IV is found in the basal lamina layer underneath epithelial tissue. It is worth pointing out that colonic tumors display higher levels of collagen IV compared to normal tissues ( Skovbjerg et al, 2009 ), which may explain a higher colonization of tumor sites by Sgg .…”

High levels of type VII collagen expression in recessive dystrophic epidermolysis bullosa cutaneous squamous cell carcinoma keratinocytes increases PI3K and MAPK signalling, cell migration and invasion

“…The role of type VII collagen in cancer is context and tissue dependent, being upregulated in some tumour types and downregulated in others . In vitro data support a context‐ and cellular‐dependent outcome after manipulating COL7A1 , yielding differing results depending on the cellular system and approaches used .…”

Genetic Predisposition to Cutaneous Squamous Cell Carcinoma

“…Up-regulation of the protein and/or mRNA is seen in esophageal SCC (Baba et al, 2006;Kita et al, 2009), colorectal carcinoma (Visser et al, 1993;Skovbjerg et al, 2009) and thyroid carcinoma (Lohi et al, 1998). In the case of esophageal SCC, increased expression of COL7A1 mRNA and its corresponding protein is correlated to a poorer five-year survival rate (Baba et al, 2006;Kita et al, 2009), while evidence in colorectal cancer suggests that the upregulation of COL7A1 mRNA and protein is an early event that occurs in both adenomas and carcinoma (Visser et al, 1993;Skovbjerg et al, 2009).…”

“…In the case of esophageal SCC, increased expression of COL7A1 mRNA and its corresponding protein is correlated to a poorer five-year survival rate (Baba et al, 2006;Kita et al, 2009), while evidence in colorectal cancer suggests that the upregulation of COL7A1 mRNA and protein is an early event that occurs in both adenomas and carcinoma (Visser et al, 1993;Skovbjerg et al, 2009).…”

“…A stronger expression in well and moderately differentiated carcinoma (Skovbjerg et al, 2009) Colorectal cancer…”