Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor.
Granulocyte-colony stimulating factor (G-CSF) produced by nonhematopoietic malignant cells has been reported to be capable of inducing a leukemoid reaction in the host through intense stimulation of leukocyte production. Furthermore, this is frequently associated with aggressive tumor cell growth 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 autocrine growth of bladder cancer cells induced by G-CSF. The cancer cells used in this study were obtained from a 76-year-old man who had a metastatic transitional cell carcinoma of the bladder and who demonstrated marked leukocytosis, his peripheral blood leukocyte count was 94,900 leukocytes/mm3, and his serum G-CSF level was 103 pg/ml. The culture medium in which the cancer cells were grown exclusively contained a significant amount of G-CSF (5560 pg/ml). Significant G-CSF mRNA expression and G-CSF receptor mRNA expression in the cultured cells were demonstrated by the reverse transcription-PCR method. In addition, binding studies with the use of radiolabeled recombinant G-CSF demonstrated the presence of high-affinity G-CSF binding receptors on the cultured cancer cells. Finally, the proliferation of the cultured cancer cells was stimulated by exogenous G-CSF administration, and this stimulation was inhibited by adding anti-G-CSF antibody, as demonstrated by both the flow cytometric bromodeoxyuridine incorporation technique and the [3H]thymidine incorporation assay. These results strongly suggest that G-CSF production by the bladder cancer cells studied augments autocrine growth. Therefore, we recommend exercising caution in the clinical use of G-CSF for bladder cancer patients.
Tachibana
M
M
Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
Miyakawa
A
A
Tazaki
H
H
Nakamura
K
K
Kubo
A
A
Hata
J
J
Nishi
T
T
Amano
Y
Y
D000368:Aged; D000818:Animals; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007964:Leukocytosis / Q000209:etiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D013936:Thymidine