Complement Factor H or a Related Protein Is a Marker for Transitional Cell Cancer of the Bladder

Robert Kinders, Tobin Jones, Richard Root, Connie Bruce, Heather Murchison, Michael Corey, Lawrence Williams, David Enfield, and G. Michael Hass

BDS, Inc., Redmond, Washington 98052 [R.K., T.J., R.R., C.B., H.M., L.W., D.E., G.M.H.] and GU Cancer Research Laboratory, University of Washington School of Medicine, Seattle, Washington 98195 [M.C.]

The BTAstat and BTA TRAK tests are new immunoassays that detect and measure an antigen in the urine of individuals diagnosed with bladder cancer. As described in this report, the monoclonal antibodies used in these kits were developed by immunizing mice with partially purified protein preparations derived from the urine of patients with bladder cancer. The antigen that is recognized by the monoclonal antibodies was purified from the urine of bladder cancer patients by immunoaffinity chromatography and identified as being either complement factor H (FH) or a closely related protein (CFHrp) by partial amino acid sequence analysis. Like serum FH, the urine antigen was demonstrated to have a complement factor C3b binding site and to accelerate the degradation of C3b in the presence of complement factor I. The culture supernatants from several human bladder, cervical, and renal cancer cell lines contained antigen as determined by immunoassay, and antigen affinity-purified from HeLaS3 culture media was shown to have FH activity. Moreover, the cell lines were shown to make products of the expected sizes by reverse 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 protein (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 cancer products also suggests avenues of chemotherapy or immunotherapy of some cancers.

Clinical Cancer Research 4: 2511-2520, October 1998.