Serum Soluble Interleukin-2 Receptor in Colorectal Cancer

Murakami, Saburo; Satomi, Akira; Ishida, Kiyoshi; Murai, Hideaki; Okamura, Y

doi:10.3109/02841869409098369

Cited by 22 publications

(18 citation statements)

References 16 publications

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“…High serum concentrations of sIL-2Ra or MMP-9 are correlated with adverse prognosis in patients with colorectal cancer, breast cancer and melanoma [20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

Agueznay

Badoual

Hans

et al. 2007

Clinical and Experimental Immunology

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SummaryIn a series of 84 head and neck patients, a statistically significant correlation was observed between high serum soluble interleukin (IL)-2 receptor alpha (sIL-2Ra) (P = 0·034) and metalloproteinase-9 (MMP-9) concentrations (P = 0·036) at diagnosis and a shorter survival of these patients. As MMP-9 has been shown to mediate cleavage of IL-2Ra (CD25) by preactivated T cells, we looked for a relationship between MMP-9 expression and soluble IL-2Ra serum concentrations in these cancer patients. We did not find any correlation between intratumoral expression of MMP-9 or serum MMP-9 concentrations and serum sIL-2Ra levels. These results led us to reassess the role of MMP-9 in the release of sIL-2Ra. Treatment of Kit225 leukaemic cells with recombinant MMP-9 slightly decreased membrane CD25 expression and was associated with an increased concentration of sIL-2Ra in the supernatants. However, using a selective inhibitor of MMP-9 we did not succeed in specifically inhibiting the release of sIL-2Ra by the Kit225 cell line or by phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells. In addition, in a preclinical mouse model, basal serum sIL-2Ra concentrations and sIL-2Ra production by activated cells were not altered in MMP-9-deficient mice compared to wild-type mice. Interestingly, a broad spectrum metalloproteinase inhibitor inhibited the release of sIL-2Ra by PHAactivated peripheral blood mononuclear cells, suggesting that in contrast with current views concerning the major role of MMP-9 in the cleavage of membrane IL-2Ra, other proteases are involved in the shedding of sIL-2Ra. MMP-9 and sIL-2Ra appear therefore as independent prognostic markers in head and neck cancers.

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“…High serum concentrations of sIL-2Ra or MMP-9 are correlated with adverse prognosis in patients with colorectal cancer, breast cancer and melanoma [20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

Agueznay

Badoual

Hans

et al. 2007

Clinical and Experimental Immunology

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“…T lymphocytes activated by IL-2 release a serum soluble form of IL-2R into the bloodstream. High levels of soluble IL-2R were observed in patients with various malignant diseases, autoimmune disorders, infections and many other inflammatory diseases [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 19, 20, 21]. There are some reports regarding the levels of IL-2R in patients with gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…1). Increased levels of serum soluble IL-2R have been found in patients with diverse diseases including lymphoma [2], lung cancer [3], gastrointestinal cancer [4, 5, 6, 7, 8], breast cancer [9], autoimmune diseases [10, 11, 12], infections [13, 14]and organ allograft rejection [15], for example. We have already reported increased concentrations of serum soluble IL-2R in patients with gastric cancer [4].…”

Section: Introductionmentioning

confidence: 99%

Serum Soluble Interleukin-2 Receptor as a Predictor of Lymph Node Metastasis in Early Gastric Cancer

Murakami

Sakata²,

Tsuji³

et al. 2002

Dig Surg

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Background: In the present study, we investigated the clinical significance of serum soluble IL-2R as a predictor of lymph node metastasis in patients with early gastric cancer. Patients and Methods: Seventy-four patients with early gastric cancer were enrolled in this study. Levels of serum soluble IL-2R were measured by an enzyme-linked immunosorbent assay. Result: Significant differences in serum soluble IL-2R between the control group and cases of T1 were not recognized. On the other hand, levels of serum soluble IL-2R in 74 patients with early gastric cancer (T1) were significantly lower than those of T2, T3, and T4 (p < 0.05). There were no significant differences in serum soluble IL-2R between cases of mucosal and submucosal invasion (379 ± 42 vs. 382 ± 35 U/ml). Six of 35 patients with submucosal invasion (17.1%) had lymph node metastasis, but none of the 39 patients with mucosal invasion. In the 6 cases showing lymph node metastasis, the macroscopic types were IIc + Ul(+) in 4, and IIc + IIa and IIc + IIb in 1, respectively. Histopathologically, there were 5 poorly and 1 moderately differentiated adenocarcinomas. In 6 cases with lymph node metastasis, serum soluble IL-2R levels were significantly higher than in those without lymph node metastasis (556.8 ± 73 vs. 329 ± 22 U/ml, respectively, mean ± SEM, p < 0.05). Five of these 6 cases demonstrated statistically significantly increased levels of serum soluble IL-2R (sensitivity 83%, specificity 63%), suggesting serum soluble IL-2R as a predictor of lymph node metastasis in early gastric cancer (p < 0.05). Conclusion: According to these data, in patients of early gastric cancer with increased levels of serum soluble IL-2R, endoscopic mucosal resection or minimal invasive gastrectomy without dissection of regional lymph nodes should be avoided, since there is a high risk of lymph node metastasis.

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“…Similar studies in various solid tumor cases have also shown sIL-2R to be an adverse prognostic feature, especially in patients with nasopharyngeal cancer [34,35], colorectal cancer [36,37], breast cancer [38], ovarian cancer [39][40][41], gastric cancer [42,43], lung cancer [44,45] and leukemia [46,47], respectively. IL-2 has been introduced as a cancer treatment since 1992.…”

Section: Interleukinmentioning

confidence: 99%