Cross linked telopeptides of type I and III collagens in malignant ovariantumours in vivo

Malignant tumours often induce a fibroproliferative response in the adjacen t stroma, characterized by increased expression of type I and type III proc ollagens. 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 ca rcinoma tissue in vivo. Biochemical and immunochemical methods were used fo r cross-linked telopeptides of type I and III collagens in samples of benig n and malignant serous tumours. The locations and staining patterns of thes e proteins were visualized immunohistochemically. The contents of both tota l collagen and the cross-linked type I and type III collagens in the malign ant samples were only about 20% of those in the benign tumours. The crossli nked telopeptide antigens derived from the collagens were smaller and more heterogeneous in size in the malignant than in the benign tumours, indicati ng a defective cross-linking process scarcely leading to the formation of m ature cross-links in the collagen fibres in malignancy. Immunostaining reve aled disorganized type I and type III collagen bundles in carcinomas. These findings suggest that the collagen cross-linking process is aberrant in ma lignant tumours, possibly resulting in increased susceptibility of tumour c ollagens for the proteolysis often associated with tumour invasion. (C)1999 Cancer Research Campaign.