AUTOCRINE GROWTH OF TRANSITIONAL-CELL CARCINOMA OF THE BLADDER INDUCED BY GRANULOCYTE-COLONY-STIMULATING FACTOR

Granulocyte-colony stimulating factor (G-CSF) produced by nonhematopoi etic malignant cells has been reported to be capable of inducing a leu kemoid reaction in the host through intense stimulation of leukocyte p roduction, Furthermore, this is frequently associated with aggressive tumor cell grow-th and a detrimental clinical outcome. In this study, we identified bladder cancer cells producing G-CSF with the expression of the functional receptor, which provides direct evidence of autocri ne growth of bladder cancer cells induced by G-CSF, The cancer cells u sed in this study were obtained from a 76-year-old man who had a metas tatic transitional cell carcinoma of the bladder and who demonstrated marked leukocytosis; his peripheral blood leukocyte count was 94,900 l eukocytes/mm(3), and his serum G-CSF level was 103 pg/ml. The culture medium in which the cancer cells were grown exclusively contained a si gnificant amount of G-CSF (5560 pg/ml), Significant G-CSF mRNA express ion and G-CSP receptor mRNA expression in the cultured cells were demo nstrated by the reverse transcription-PCR method. In addition, binding studies with the use of radiolabeled recombinant G-CSF demonstrated t he presence of high-affinity G-CSF binding receptors on the cultured c ancer cells, Finally, the proliferation of the cultured cancer cells w as stimulated by exogenous G-CSF administration, and this stimulation was inhibited by adding anti-G-CSF antibody, as demonstrated by both t he flow cytometric bromodeoxyuridine incorporation technique and the [ H-3]thymidine incorporation assay, These results strongly suggest that G-CSF production by the bladder cancer cells studied augments autocri ne growth. Therefore, we recommend exercising caution in the clinical use of G-CSF for bladder cancer patients.