Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, PR China.
Pancreas. 2011 Jul;40(5):753-61. doi: 10.1097/MPA.0b013e318213d51b.
To investigate the expression of Igγ-1 chain C region (IGHG1) in human pancreatic carcinomas and determine the biological function of IGHG1 expression in immune evasion mechanisms.
Comparative proteomic analysis was used to detect the differential expression of IGHG1 in human pancreatic cancer tissues versus adjacent noncancerous tissues, followed by confirmatory tests including quantitative real-time reverse transcription-polymerase chain reaction, Western blot analysis, immunohistochemistry, and immunofluorescence. A murine pancreatic tumor model was established by transplantation of IGHG1-overexpressing Panc02 cells. The cytotoxic responses of natural killer (NK) cells were assessed with a lactate dehydrogenase release assay.
Igγ-1 chain C region was found to be present in human pancreatic cancer tissues but nearly absent or expressed lower in adjacent noncancerous tissues. In the murine pancreatic tumor model, the tumor growth was significantly accelerated from day 12 to 20 after tumor injection, and the survival time of animals was decreased. Blockage of IGHG1 led to retarded tumor growth and improved survival. The cytotoxicity assay revealed that IGHG1 downregulated the cytotoxic activity of NK cells through inhibition of antibody-dependent cellular cytotoxicity function.
The presence of IGHG1 in pancreatic cancer cells might constitute an important element responsible for tumor cell proliferation and immune evasion mechanisms.
研究 Igγ-1 链 C 区（IGHG1）在人胰腺癌细胞中的表达情况，并确定 IGHG1 表达在免疫逃逸机制中的生物学功能。
采用比较蛋白质组学分析方法检测人胰腺癌细胞组织与相邻非癌组织中 IGHG1 的差异表达，随后进行定量实时逆转录-聚合酶链反应、Western blot 分析、免疫组织化学和免疫荧光验证。通过移植过表达 IGHG1 的 Panc02 细胞建立小鼠胰腺肿瘤模型。采用乳酸脱氢酶释放法评估自然杀伤（NK）细胞的细胞毒性反应。
在人胰腺癌细胞组织中发现存在 Igγ-1 链 C 区，但在相邻非癌组织中几乎不存在或表达水平较低。在小鼠胰腺肿瘤模型中，自肿瘤注射后第 12 天至第 20 天，肿瘤生长明显加快，动物的生存时间缩短。阻断 IGHG1 导致肿瘤生长减缓，生存时间延长。细胞毒性测定显示，IGHG1 通过抑制抗体依赖的细胞毒性功能下调 NK 细胞的细胞毒性活性。
IGHG1 在胰腺癌细胞中的存在可能构成肿瘤细胞增殖和免疫逃逸机制的重要因素。
