Expression and secretion of the beta subunit of
human chorionic gonadotropin (hCG) by bladder
carcinoma cell lines were investigated in vitro and in vivo. As an in vitro study, immunoreactive
hCG beta (IR-
hCG beta) secreted into the
culture media of two bladder transitional cell lines (KoTCC-1 and HT-1197) was analyzed using three kinds of
enzyme immunoassays which were specific for intact hCG, free
hCG beta, and beta
core fragment (beta-CF). Both of the cell lines were determined to secrete IR-
hCG beta into the media, which consisted principally of free
hCG beta, but detectable levels of intact hCG and beta-CF were not present in the media. Northern blot analysis revealed that the
hCG beta gene was expressed in both KoTCC-1 and HT-1197 cells where the sizes of
mRNA from these cells were smaller than those from placental and NJG
choriocarcinoma cells. As an in vivo study, distribution of IR-
hCG beta was analyzed in the
tumor tissues, sera, and urine of the mice and the rats transplanted with KoTCC-1 cells. By the immunohistochemical study, the IR-
hCG beta was clearly observed in
transitional cell carcinoma cells of the transplanted
tumor. High levels of IR-
hCG beta were detected in both the serum and urine from the animals, but there were quantitative and qualitative differences between serum and urinary IR-
hCG beta. Quantitatively, the concentrations of IR-
hCG beta in the urine were consistently much higher than those in the serum. Qualitatively, free
hCG beta was exclusively detected in the serum whereas high levels of beta-CF in addition to free
hCG beta were found in the urine. Intact hCG could not be detected in the serum and urine. These distributions of IR-
hCG beta in the animals transplanted with KoTCC-1 cells were completely analogous to those in a patient with
hCG beta-producing bladder
carcinoma. The present study shows that the same metabolic pathway of IR-
hCG beta is operating in mice and rats as in humans, indicating that IR-
hCG beta found in patients with bladder
carcinoma originates from the
tumor and it may be recognized as a
tumor marker when beta-CF is measured in the patient's urine.