Identification of HLA-A*2402-restricted epitope peptide derived from ERas oncogene expressed in human scirrhous gastric cancer
Identification of HLA-A*2402-restricted epitope peptide derived from ERas oncogene expressed in human scirrhous gastric cancer
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DOI：
10.1111/j.1349-7006.2010.01843.x
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发表时间：
2011-04-01
期刊：
影响因子：
5.7
通讯作者：
Hirakawa, Kosei
中科院分区：
文献类型：
--
作者：
Iwauchi, Takehiko;Tanaka, Hiroaki;Hirakawa, Kosei
ERAS是新近发现的一种参与胚胎干细胞致瘤性生长的癌基因。我们研究了ERAS在硬化性胃癌中表达的意义，以及ERAS作为胃癌肿瘤相关抗原的可能性，以开发一种癌症疫苗。采用免疫组织化学方法检测硬化性胃癌组织中ERAS的表达。为了评估ERAS蛋白作为抗癌疫苗靶点的可能性，我们检查了人类白细胞抗原A限制性表位多肽的ERAS是否能够激发细胞毒性T淋巴细胞活性。免疫组织化学检测发现癌细胞胞核和胞浆均有ERAS蛋白表达，而正常胃上皮不表达ERAS蛋白。经Western blotting检测，硬化性胃癌细胞株OCUM-8、OCUM-2MD3和OCUM-2M的裂解产物均含有一条25 kDa的Era蛋白条带。RT-PCR检测到ERAS基因在这些细胞系中的表达。为了研究细胞毒性，我们成功地建立了由人类白细胞抗原-A*2402限制性反式表位多肽刺激的细胞毒性T淋巴细胞克隆(FALDDPSSL)。这些多肽对候选多肽冲击的相应的HLA-A*2402阳性靶细胞具有特异性的细胞毒作用。我们发现，细胞毒性T淋巴细胞克隆对内源性表达ERAS的OCUM-8细胞具有细胞毒活性。我们的结果提示ERAS是一种新的肿瘤相关抗原，有可能作为疫苗应用于硬化性胃癌。(《癌症科学》2011；102：683-689)
ERas is a recently identified oncogene involved in the tumorgenic growth of embryonic stem cells. We examined the significance of ERas expression in scirrhous gastric carcinoma, and the possibility of ERas as a tumor-associated antigen of gastric cancer for developing a cancer vaccine. ERas expression was determined in scirrhous gastric carcinoma specimens by immunohistochemical staining. To assess the possibility of the ERas protein as an anticancer vaccine target, we examined whether ERas for HLA-A-restricted epitope peptides were capable of eliciting cytotoxic T lymphocyte activity. Immunohistochemical analysis identified ERas protein in the nucleus and cytoplasm of cancer cells, yet ERas was not expressed in normal gastric epithelium. By western blotting, lysates of the scirrhous gastric cancer cell lines, OCUM-8, OCUM-2MD3 and OCUM-2M were shown to contain a 25-kDa band of ERas protein. ERas mRNA was detected in these cell lines by RT-PCR. To investigate cytotoxicity, we successfully established cytotoxic T lymphocyte clones stimulated by HLA-A*2402-restricted ERas peptides (FALDDPSSL). These peptides have specific cytotoxicity against corresponding HLA-A*2402-positive target cells pulsed with the candidate peptide. We found that the cytotoxic T lymphocyte clones demonstrated cytotoxic activity against OCUM-8 cells that endogenously express ERas. Our results suggest that ERas is a novel tumor-associated antigen with the potential application to be a vaccine against scirrhous gastric cancer. (Cancer Sci 2011; 102: 683-689)