Mesothelin expression in human lung cancer
Mesothelin expression in human lung cancer
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DOI：
10.1158/1078-0432.ccr-06-2161
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发表时间：
2007-03-01
影响因子：
11.5
通讯作者：
Pastan, Ira
中科院分区：
文献类型：
--
作者：
Ho, Mitchell;Bera, Tapan K.;Pastan, Ira
目的：探讨间充质蛋白作为肺癌免疫治疗的新靶点。实验设计：采用逆转录-聚合酶链式反应、免疫印迹和免疫组织化学方法检测人肺癌组织中间充质蛋白基因和蛋白的表达。用流式细胞仪和免疫印迹法检测其在人肺癌细胞系中的表达。结果：我们发现83%的肺腺癌(10/12例)中有间皮蛋白基因的表达。在11例肺腺癌组织中，82%(9/11)的肺腺癌组织中检测到间皮样前体蛋白，6例(6/11)的肺腺癌组织中检测到成熟蛋白。免疫组织化学显示，人肺腺癌中间皮蛋白呈强阳性和弥漫性阳性，鳞癌中弱阳性或中等阳性。我们在NCL-60细胞组中78%的肺癌细胞株(7/9)中检测到间皮素基因的表达。非小细胞肺癌细胞株EKVX、NCL-H460、NCL-H322M和NCL-H522均高水平表达间皮蛋白。流式细胞仪分析显示NCL-H322M和EKVX细胞系表面高表达间皮蛋白。免疫毒素SS1P对NCL-H322M和EKVX细胞具有较高的细胞毒活性，IC50值在2~5 ng/ml之间。免疫毒素SS1P对表达间充质蛋白的肺癌细胞株具有细胞毒作用，可作为治疗非小细胞肺癌的新药物。
Purpose: To investigate mesothelin as a new target for immunotherapy in lung cancer.Experimental Design: Mesothelin mRNA and protein expression were assessed by reverse transcription-PCR, immunoblotting, and immunohistochemistry in human lung cancer specimens. Expression was also characterized in human lung cancer cell lines by flow cytometry and immunoblotting. The SS1P immunotoxin specific for mesothelin was assessed for its cytotoxic activity against lung cancer cells.Results: We found that mesothelin mRNA was expressed in 83% of lung adenocarcinomas (10 of 12 patients). The mesothelin precursor protein was detected in 82% of lung adenocarcinoma (9 of 11 patients), and its mature form was detected in 55% (6 of 11 patients). Immunohistochemistry showed strong and diffuse mesothelin staining in human lung adenocarcinomas and weak or modest staining in squamous cell carcinomas. We detected mesothelin mRNA in 78% of lung cancer cell lines (7 of 9) of the NCl-60 cell line panel. Mesothelin mRNA and proteins were expressed at a high level in non-small cell lung cancer lines EKVX, NCl-H460, NCl-H322M, and NCl-H522. Flow cytometric analysis showed high surface expression of mesothelin in NCl-H322M and EKVX cell lines. Immunotoxin SS1P showed high cytotoxic activity on NCl-H322M and EKVX cells with IC50 values ranging from 2 to 5 ng/mL.Conclusions: Mesothelin is expressed on the surface of most lung adenocarcinoma cells. Immunotoxin SS1P is cytotoxic against mesothelin-expressing lung cancer cell lines and merits evaluation as a new therapeutic agent in treating non-small cell lung cancer.