Tissue-infiltrating plasma cells are an important source of carboxylesterase 2 contributing to the therapeutic efficacy of prodrugs
Tissue-infiltrating plasma cells are an important source of carboxylesterase 2 contributing to the therapeutic efficacy of prodrugs
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DOI：
10.1016/j.canlet.2016.04.041
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发表时间：
2016-08-01
期刊：
影响因子：
9.7
通讯作者：
Utku, Nalan
中科院分区：
文献类型：
--
作者：
Kuehl, Anja A.;Erben, Ulrike;Utku, Nalan
羧酸酯酶 2 (CES-2) 在癌症治疗中有助于转化含酯前药。通过免疫组织化学分析结直肠癌 (CRC) 与结肠炎症以及肝脏和外周血中的 CES-2 表达。在 CRC 中，肿瘤分级与 CES-2 表达水平没有相关性，这些肿瘤内的 CES-2 表达水平是异质的。肿瘤附近的细胞浸润表达高水平的 CES-2。因此，邻近肿瘤的组织是浆细胞中高表达的CES-2的重要来源。在炎症性肠病患者的结肠中发现大量 CES-2（高）浆细胞。 CES-2在正常肝脏的肝细胞中表达较强，而健康供体外周血单个核细胞中CES-2的蛋白和mRNA表达水平总体较低。综上所述，CES-2对含酯前药的转化主要发生在外周、肝传代过程中以及肠肝再循环后的结肠中。我们在此证明浆细胞是 CES-2 的强大生产者。进一步的研究应该阐明 CES-2(+) 浆细胞在肠道炎症和癌症中的作用。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
Carboxylesterase 2 (CES-2) is instrumental for conversion of ester-containing prodrugs in cancer treatment. CES-2 expression was analyzed by immunohistochemistry in colorectal cancer (CRC) compared to colonic inflammation as well as in liver and peripheral blood.In CRC, tumor grades showed no correlation with levels of CES-2 expression, which was heterogeneous within these tumors. Cellular infiltrates in the immediate tumor vicinity expressed high levels of CES-2. Thus, tissue adjacent to the tumor was a substantial source of CES-2 with high expression in plasma cells. CES-2(high) plasma cells were abundantly found in the colon of patients with inflammatory bowel disease. CES-2 expression is strong in hepatocytes of normal livers, while CES-2 expression in peripheral blood mononuclear cells of healthy donors was overall low at protein and mRNA levels.In summary, the conversion of ester-containing prodrugs by CES-2 is mainly to occur in the periphery, during liver passage and in the colon after enterohepatic recirculation. We here demonstrated plasma cells as strong producers of CES-2. Further studies should elucidate the role of CES-2(+) plasma cells in intestinal inflammation and cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.