COMPLEMENT FACTOR-H OR A RELATED PROTEIN IS A MARKER FOR TRANSITIONAL-CELL CANCER OF THE BLADDER

The BTAstat and BTA TRAK tests are new immunoassays that detect and me asure an antigen in the urine of individuals diagnosed with bladder ca ncer. As described in this report, the monoclonal antibodies used in t hese kits were developed by immunizing mice with partially purified pr otein preparations derived from the urine of patients with bladder can cer. The antigen that is recognized by the monoclonal antibodies was p urified from the urine of bladder cancer patients by immunoaffinity ch romatography and identified as being either complement factor H (FH) o r a closely related protein (CFHrp) by partial amino acid sequence ana lysis, Like serum FH, the urine antigen was demonstrated to have a com plement factor C3b binding site and to accelerate the degradation of C 3b in the presence of complement factor I. The culture supernatants fr om several human bladder, cervical, and renal cancer cell lines contai ned antigen as determined by immunoassay, and antigen affinity-purifie d from HeLaS3 culture media was shown to have FH activity. Moreover, t he cell lines were shown to make products of the expected sizes by rev erse transcription-PCR using FH-specific primers. In contrast, normal human epithelial keratinocytes, a myeloid leukemia cell line, and the colon cancer line LS174T were negative for production of a FH-like pro tein (CFHrp). We propose that the expression of proteins with FH-like activities may confer a selective growth advantage to cancer cells in vivo by decreasing complement activity, thus aiding their escape from lysis by immune surveillance. Identification of these proteins as canc er products also suggests avenues of chemotherapy or immunotherapy of some cancers.