Cross-linked telopeptides of type I and III collagens in malignant ovarian tumours in vivo.
Malignant tumours often induce a fibroproliferative response in the adjacent stroma, characterized by increased expression of type I and type III procollagens. In normal tissues, fibrillar collagens normally undergo extensive intermolecular cross-linking that provides tensile strength to the tissue. Here we set out to characterize collagen cross-linking in human ovarian carcinoma tissue in vivo. Biochemical and immunochemical methods were used for cross-linked telopeptides of type I and III collagens in samples of benign and malignant serous tumours. The locations and staining patterns of these proteins were visualized immunohistochemically. The contents of both total collagen and the cross-linked type I and type III collagens in the malignant samples were only about 20% of those in the benign tumours. The cross-linked telopeptide antigens derived from the collagens were smaller and more heterogeneous in size in the malignant than in the benign tumours, indicating a defective cross-linking process scarcely leading to the formation of mature cross-links in the collagen fibres in malignancy. Immunostaining revealed disorganized type I and type III collagen bundles in carcinomas. These findings suggest that the collagen cross-linking process is aberrant in malignant tumours, possibly resulting in increased susceptibility of tumour collagens for the proteolysis often associated with tumour invasion.
Kauppila
S
S
Department of Clinical Chemistry, University of Oulu, Finland.
Bode
M K
MK
Stenbäck
F
F
Risteli
L
L
Risteli
J
J
D003094:Collagen / Q000032:analysis* / Q000737:chemistry; D024042:Collagen Type I; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000737:chemistry*; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides / Q000032:analysis; D011347:Procollagen / Q000032:analysis
D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen; D006909:Hydroxyproline