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Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer.

Okugawa Y, Miki C, Toiyama Y, Yasuda H, Yokoe T, Saigusa S, Hiro J, Tanaka K, Inoue Y, Kusunoki M - Br. J. Cancer (2010)

Bottom Line: Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation.In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

ABSTRACT

Background: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients.

Methods: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis.

Results: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.

Conclusion: Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

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Correlation between the sIL-6R Ca/N expression ratio and the IL-1β Ca/N expression ratio. sIL-6R Ca/N expression ratio was positively correlated with the IL-1β Ca/N expression ratio.
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fig6: Correlation between the sIL-6R Ca/N expression ratio and the IL-1β Ca/N expression ratio. sIL-6R Ca/N expression ratio was positively correlated with the IL-1β Ca/N expression ratio.

Mentions: The concentrations of IL-1β in cancer tissues ranged from 0.845 to 757 pg per mg protein, with a mean level of 37.8±80.2 pg per mg protein. The concentrations of IL-1β in normal mucosa ranged from 0.38 to 79.4 pg per mg protein, with a mean level of 8.69±10.4 pg per mg protein. The ratio between the concentrations of IL-1β in cancer tissue and normal mucosa (IL-1β Ca/N ratio: cancer tissue IL-1β concentration divided by normal mucosa IL-1β concentration) ranged from 0.86 to 116 with a mean value of 6.75±10.8. The tumoral IL-1β Ca/N expression ratio was positively correlated with sIL-6R Ca/N expression ratio (Wilcoxon Signed-rank test, P<0.001) (Figure 6).


Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer.

Okugawa Y, Miki C, Toiyama Y, Yasuda H, Yokoe T, Saigusa S, Hiro J, Tanaka K, Inoue Y, Kusunoki M - Br. J. Cancer (2010)

Correlation between the sIL-6R Ca/N expression ratio and the IL-1β Ca/N expression ratio. sIL-6R Ca/N expression ratio was positively correlated with the IL-1β Ca/N expression ratio.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966622&req=5

fig6: Correlation between the sIL-6R Ca/N expression ratio and the IL-1β Ca/N expression ratio. sIL-6R Ca/N expression ratio was positively correlated with the IL-1β Ca/N expression ratio.
Mentions: The concentrations of IL-1β in cancer tissues ranged from 0.845 to 757 pg per mg protein, with a mean level of 37.8±80.2 pg per mg protein. The concentrations of IL-1β in normal mucosa ranged from 0.38 to 79.4 pg per mg protein, with a mean level of 8.69±10.4 pg per mg protein. The ratio between the concentrations of IL-1β in cancer tissue and normal mucosa (IL-1β Ca/N ratio: cancer tissue IL-1β concentration divided by normal mucosa IL-1β concentration) ranged from 0.86 to 116 with a mean value of 6.75±10.8. The tumoral IL-1β Ca/N expression ratio was positively correlated with sIL-6R Ca/N expression ratio (Wilcoxon Signed-rank test, P<0.001) (Figure 6).

Bottom Line: Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation.In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

ABSTRACT

Background: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients.

Methods: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis.

Results: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.

Conclusion: Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

Show MeSH
Related in: MedlinePlus