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

Hyogo Institute of Clinical Research, 13-70 Kitaoji-cho, Akashi 673 [R. N., T. K., K. M., R. L., M. Y., T. N., K. S., K. H., S. B.], and Department of Urology, Shinko Hospital, Nada-ku, Kobe 651 [N. Y.], Japan

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

¹ This work was supported by Grant-in-Aid 4-18 for Cancer Research from the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 9/19/94. Accepted 2/ 3/95.