Expression and Secretion of the β Subunit of Human Chorionic Gonadotropin by Bladder Carcinoma in Vivo and in Vitro¹ Free

Expression and secretion of the β subunit of human chorionic gonadotropin (hCG) by bladder carcinoma cell lines were investigated in vitro and in vivo. As an in vitro study, immunoreactive hCGβ (IR-hCGβ) 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 hCGβ, and β core fragment (β-CF). Both of the cell lines were determined to secrete IR-hCGβ into the media, which consisted principally of free hCGβ, but detectable levels of intact hCG and β-CF were not present in the media. Northern blot analysis revealed that the hCGβ 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-hCGβ 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-hCGβ was clearly observed in transitional cell carcinoma cells of the transplanted tumor. High levels of IR-hCGβ were detected in both the serum and urine from the animals, but there were quantitative and qualitative differences between serum and urinary IR-hCGβ. Quantitatively, the concentrations of IR-hCGβ in the urine were consistently much higher than those in the serum. Qualitatively, free hCGβ was exclusively detected in the serum whereas high levels of β-CF in addition to free hCGβ were found in the urine. Intact hCG could not be detected in the serum and urine. These distributions of IR-hCGβ in the animals transplanted with KoTCC-1 cells were completely analogous to those in a patient with hCGβ-producing bladder carcinoma. The present study shows that the same metabolic pathway of IR-hCGβ is operating in mice and rats as in humans, indicating that IR-hCGβ found in patients with bladder carcinoma originates from the tumor and it may be recognized as a tumor marker when β-CF is measured in the patient's urine.