INCREASED FRAGMENTATION OF URINARY FIBRONECTIN IN CANCER-PATIENTS DETECTED BY IMMUNOENZYMOMETRIC ASSAY USING DOMAIN-SPECIFIC MONOCLONAL-ANTIBODIES

Monoclonal antibodies (MoAbs) recognizing the distinct domains of huma n fibronectin had previously been established and they were used to co nstruct several sandwich immunoenzymometric assays (IEMAs) for the str uctural analysis of fibronectin found in the urine of cancer patients. Urinary fibronectin (UFN) was immunodetectable only with FN12-8 and F N30-8 MoAbs against cell-binding domains and was less reactive with ot her IEMAs using MoAbs directed to terminal domains, indicating that UF N was almost completely fragmented and consisted mainly of cell-bindin g regions. The IEMA using MoAbs against cell-binding domains had suffi cient immunoreactivities with the antigen fragmented by artificial pro teolysis, but these fragments could hardly be detected by other IEMAs. UFN levels were significantly elevated in various cancer patients and extremely elevated in some patients with distant metastasis. It is pr esumed that UFN fragments which increase in cancer patients are genera ted by extracellular matrix destruction. Thus UFN levels and the ratio of the fragmented UFN level to the non-fragmented UFN level appear to be informative clinical indicators of tumor malignancy or metastatic ability in cancer patients.