Interleukin-6 Activity in Urine and Serum in Patients with Bladder Carcinoma

Seguchi, T; Yokokawa, Kiyoshi; Sugao, Hideki; Nakano, Etsuji; Sonoda, T; Okuyama, Äkïhïko

doi:10.1016/s0022-5347(17)36721-6

Cited by 49 publications

(24 citation statements)

References 16 publications

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“…The results of clinical investigations seem to support this concept in that the IL-6 concentration in urine correlates with the stage of bladder cancer and IL-6 is absent after tumor resection (Seguchi et al, 1992).…”

Section: Discussionmentioning

confidence: 72%

“…Several human bladder carcinoma cell lines have been reported to secrete IL-6 (Meyers et al, 1991;de Reijke et al, 1993), and IL-6 levels in urine and serum increase in patients with bladder cancer (Seguchi et al, 1992). Thus, we hypothesized that IL-6 acts as an autocrine growth factor in bladder carcinoma cells.…”

Section: Discussionmentioning

confidence: 97%

“…Meyers et al (1991) reported that specific mRNAs for both IL-6 and IL-6 receptor were expressed in de novo bladder carcinomas and bladder carcinoma cell lines. Several investigators also have demonstrated that bladder carcinoma cells produced and released IL-6 in vivo and in vitro (Seguchi et al, 1992;de Reijke et al, 1993;Rawle et al, 1986).In the present study, to examine whether IL-6 acts as an autocrine growth factor for normal and neoplastic urothelial cells, we conducted an in vitro experiment by using primary cultures of normal urothelial cells and bladder carcinoma cell lines. …”

mentioning

confidence: 96%

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Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell linesin vitro

Okamoto¹,

Hattori²,

Oyasu³

1997

Int. J. Cancer

234

258

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Interleukin (IL)-6 is reported to function as a growth factor for renal and prostatic carcinomas. We conducted the present study to define the role of IL-6 in the growth of normal and neoplastic urothelial cells. Human bladder carcinoma cell lines (253J, RT4 and T24) and primary cultured human urothelial cells derived from normal ureters were used. Recombinant human IL-6 stimulated the growth of bladder carcinoma cell lines far better than that of normal urothelial cells (p F 0.001). All carcinoma cell lines tested produced and released IL-6, whereas normal urothelial cells did so only at marginal levels. Furthermore, treatment with lipopolysaccharide derived from Escherichia coli, tumor necrosis factor-a or IL-1 increased IL-6 secretion by bladder carcinoma cell lines but not by normal urothelial cells. Growth of bladder carcinoma cells was significantly inhibited by anti-IL-6 neutralizing antibody or the anti-sense oligonucleotide for IL-6 cDNA. We conclude that IL-6 functions as an autocrine growth factor for bladder carcinoma cells but not for normal urothelial cells and that it may be a factor accounting for the marked enhancement of inflammation-associated bladder carcinogenesis and tumor growth. Interleukin (IL)-6, originally identified as a T cell-derived cytokine that induces final maturation of B cells into antibodyproducing cells , exhibits multiple biologic activities that differ widely among various types of tissue and cell. IL-6 can enhance or inhibit the proliferation of carcinoma cells (Eustace et al., 1993;Miki et al., 1989;Tam et al., 1989). A variety of malignant tumors, including squamous-cell carcinomas and adenocarcinomas, have been shown to contain or synthesize IL-6, and autocrine growth stimulation has been suggested as the mechanism for IL-6 action (Eustace et al., 1993;Lu and Kerbel, 1993). In the genito-urinary system, IL-6 functions as an autocrine growth factor for renal-cell and prostatic carcinomas (Miki et al., 1989;Takenawa et al., 1991;Borsellino et al., 1995;Okamoto et al., 1997).We have shown that a continuous inflammatory stimulus strikingly accelerates N-methyl-N-nitrosourea-initiated rat urinary bladder carcinogenesis (Yamamoto et al., 1992;Kawai et al., 1993Kawai et al., , 1994 and that transformation in vitro can be enhanced significantly by IL-6 treatment (Okamoto et al., 1995). Furthermore, we observed that IL-6 released by inflammatory cells and bladder stromal cells could greatly stimulate the growth of non-tumorigenic and tumorigenic rat urothelial cell lines that did not secrete IL-6 and that transfected IL-6 markedly accelerated the growth rate of low-tumorigenicity rat urothelial cells ; data not shown). These findings suggest that IL-6 functions as a paracrine growth factor for bladder epithelial cells in vitro.Several reports, however, suggest that IL-6 is an autocrine growth factor in bladder cancer. Meyers et al. (1991) reported that specific mRNAs for both IL-6 and IL-6 receptor were expressed in de novo bladder carcinomas and bladder carcinoma cell lines. S...

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 96%

See 1 more Smart Citation

Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell linesin vitro

Okamoto¹,

Hattori²,

Oyasu³

1997

Int. J. Cancer

234

258

View full text Add to dashboard Cite

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“…IL-6 is also reported to be produced by other epithelial tumors [5]. Increased serum IL-6 levels have been found in patients with multiple myeloma [6], renal cell carcinoma [7], bladder carcinoma [8], head and neck cancer [9], ovarian cancer [10], and cholangiocarcinoma [11].…”

Section: Introductionmentioning

confidence: 99%

Serum interleukin-6 and -10 levels in patients with gastric cancer

et al. 2009

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“…In vitro study demonstrated that urothelial malignant cells secrete a large amount of IL-6 compared to normal urothelium, and the addition of anti-IL-6 antibody and antisense oligonucleotide significantly reduced cancerous cell growth [23]. Simultaneously, significant elevated levels of IL-6 were reported in urine of UBC patients [24]. Cardillo et al [25] reported by immuno-histochemistry expression that high-grade and muscle-invasive bladder tumors contained significantly higher levels of IL-6 proteins.…”

Section: Pro-and Anti-inflammatory Cytokines Gene Variants and Their mentioning

confidence: 99%

Gene Variants in Predicting BCG Response to Urinary Bladder Cancer

Mittal

2012

Ind J Clin Biochem

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Interleukin-6 Activity in Urine and Serum in Patients with Bladder Carcinoma

Cited by 49 publications

References 16 publications

Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell linesin vitro

Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell linesin vitro

Serum interleukin-6 and -10 levels in patients with gastric cancer

Gene Variants in Predicting BCG Response to Urinary Bladder Cancer

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