Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas
Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas
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DOI：
10.1007/s10434-001-0458-x
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发表时间：
2001-06-01
影响因子：
3.7
通讯作者：
Tanaka, M
中科院分区：
文献类型：
--
作者：
Kojima, M;Morisaki, T;Tanaka, M
背景：前列腺素E可影响抗肿瘤淋巴细胞反应，引起肿瘤部位的局部免疫抑制。环氧合酶(COX)是前列腺素E合成的关键酶，其作用机制尚不清楚。我们检测了环氧合酶(COX)-2是否参与了人结肠癌细胞株和临床肿瘤标本的局部免疫抑制。方法：测定高表达COX-2的人结肠癌细胞系(CE-1)和其他细胞系培养上清液中PGE的浓度。用有丝分裂原对淋巴细胞增殖的反应来评估肿瘤细胞-淋巴细胞在有或没有选择性COX-2抑制剂NS-398的共同培养中的免疫抑制。采用逆转录聚合酶链式反应(RT-PCR)检测COX-2mRNA在结直肠癌手术标本中的表达，用免疫组织化学方法检测COX-2蛋白的表达，分析COX-2表达与临床病理特征的关系。结果：CE-1细胞产生大量PGE(2)，NS-398对其有明显的抑制作用。与CE-1细胞共培养的淋巴细胞的增殖指数明显低于对照淋巴细胞；NS-398也抑制了这一作用。结直肠癌组织中COX-2的表达高于非肿瘤组织，但COX-2的表达水平与结肠癌的临床病理特征无明显相关性。结论：结肠癌组织中COX-2的过度表达可能导致局部免疫抑制，COX-2抑制剂可能对结肠癌有治疗作用。
Background: Prostaglandin (PG) E, has an influence on antitumor lymphocyte reactions and causes local immunosuppression at tumor sites. The contribution of cyclooxygenase (COX), a key enzyme in PGE, synthesis, to this effect is still unclear. We examined if cyclooxygenase (COX)-2 is involved in local immunosuppression in human colon carcinoma cell lines and in clinical tumor specimens.Methods: PGE, concentrations were measured in culture media from a highly COX-2-expressing human colon carcinoma cell line (CE-1) and other cell lines. Lymphocyte proliferation in response to a mitogen was used to evaluate immunosuppression in tumor cell-lymphocyte cocultures with and without selective COX-2 inhibitor NS-398. We also evaluated expression of COX-2 mRNA in surgical specimens of colorectal carcinoma by reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein by immunohistochemistry, correlating COX-2 expression with clinicopathologic features.Results: CE-1 cells produced large amounts of PGE(2), which was significantly inhibited by NS-398. The proliferation index of lymphocytes cocultured with CE-1 cells was significantly less than that of control lymphocytes; again, this effect was inhibited by NS-398. While human colorectal carcinoma tissue expressed more COX-2 mRNA and protein than nonneoplastic tissue, no significant correlation was found between COX-2 levels and clinicopathologic features.Conclusions: Overexpression of COX-2 in colon cancer may cause local immunosuppressisn, and COX-2 inhibitors might be therapeutically useful against these tumors.