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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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Related in: MedlinePlus

(A) Scattergram of the sIL-6R Ca/N expression ratios with UICC classification in 161 colorectal cancer patients. (B) Scattergram of the sIL-6R Ca/N expression ratios with T classification in 161 colorectal cancer patients.
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fig1: (A) Scattergram of the sIL-6R Ca/N expression ratios with UICC classification in 161 colorectal cancer patients. (B) Scattergram of the sIL-6R Ca/N expression ratios with T classification in 161 colorectal cancer patients.

Mentions: The mean level of the sIL-6R Ca/N expression ratios in stage I patients was significantly higher than those in stage II, III or IV patients (Figure 1A). Table 1 shows the relationship between the sIL-6R Ca/N expression ratio and clinicopathological findings. Loss of tumoral sIL-6R expression was associated with factors showing disease progression, such as T classification, the presence of distant metastasis, and the progression of UICC classification. In addition, the mean level of the sIL-6R Ca/N expression ratio in the T2 patients was significantly higher than the levels in T3 or T4 patients (Figure 1B).


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)

(A) Scattergram of the sIL-6R Ca/N expression ratios with UICC classification in 161 colorectal cancer patients. (B) Scattergram of the sIL-6R Ca/N expression ratios with T classification in 161 colorectal cancer patients.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: (A) Scattergram of the sIL-6R Ca/N expression ratios with UICC classification in 161 colorectal cancer patients. (B) Scattergram of the sIL-6R Ca/N expression ratios with T classification in 161 colorectal cancer patients.
Mentions: The mean level of the sIL-6R Ca/N expression ratios in stage I patients was significantly higher than those in stage II, III or IV patients (Figure 1A). Table 1 shows the relationship between the sIL-6R Ca/N expression ratio and clinicopathological findings. Loss of tumoral sIL-6R expression was associated with factors showing disease progression, such as T classification, the presence of distant metastasis, and the progression of UICC classification. In addition, the mean level of the sIL-6R Ca/N expression ratio in the T2 patients was significantly higher than the levels in T3 or T4 patients (Figure 1B).

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