Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer
Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer
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甲状腺乳头状癌中免疫球蛋白 G 的表达及其与补体蛋白的共定位
DOI：
10.1038/modpathol.2011.139
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发表时间：
2012-01-01
期刊：
影响因子：
7.5
通讯作者：
Gu, Jiang
中科院分区：
文献类型：
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作者：
Qiu, Yamei;Korteweg, Christine;Gu, Jiang
除了已知的产生免疫球蛋白G（IgG）的细胞类型，即成熟的B淋巴细胞和浆细胞，已经发现各种非淋巴样细胞类型，包括人癌细胞、神经元和一些特定的上皮细胞表达IgG。本研究检测了甲状腺乳头状癌细胞IgG重链（IgG γ）和κ轻链（IG kappa）的表达。应用原位杂交技术检测甲状腺乳头状癌细胞中人IgG 1恒定区（IGHG 1）的表达。用激光捕获显微切割和RT-PCR技术，从甲状腺乳头状癌细胞中成功扩增出IGHG 1、IG κ、重组激活基因1（RAG 1）、RAG 2和激活诱导的胞苷脱氨酶基因的mRNA转录产物。我们进一步用免疫组化证实IgG蛋白表达，发现IgG受体在甲状腺乳头状癌中均不表达。IgG γ表达水平在肿瘤大小之间、乳头状甲状腺癌与正常甲状腺组织之间以及有无淋巴结转移的乳头状甲状腺癌之间差异显著。综上所述，这些结果表明IgG是由乳头状甲状腺癌细胞产生的，并且它可能与乳头状甲状腺癌细胞的生长和转移呈正相关。此外，证明IgG γ与补体蛋白共定位在相同的癌细胞中，这可以表明形成了免疫复合物。这种免疫复合物可能由宿主针对肿瘤表面抗原合成的IgG和局部产生的对这些“一级”抗体的可变区具有特异性的抗独特型IgG组成。因此，癌细胞可能逃避宿主肿瘤抗原特异性免疫应答，从而促进肿瘤进展。Modern Pathology（2012）25，36-45; doi：10.1038/modpathol.2011.139; 2011年9月9日在线发表
Except for the well-known immunoglobulin G (IgG) producing cell types, ie, mature B lymphocytes and plasma cells, various non-lymphoid cell types, including human cancer cells, neurons, and some specified epithelial cells, have been found to express IgG. In this study, we detected the expression of the heavy chain of IgG (IgG gamma) and kappa light chain (Ig kappa) in papillary thyroid cancer cells. Using in situ hybridization, we detected the constant region of human IgG1 (IGHG1) in papillary thyroid cancer cells. With laser capture microdissection followed by RT-PCR, mRNA transcripts of IGHG1, Ig kappa, recombination activating gene 1 (RAG1), RAG2, and activation-induced cytidine deaminase genes were successfully amplified from isolated papillary thyroid cancer cells. We further confirmed IgG protein expression with immunohistochemistry and found that none of the IgG receptors was expressed in papillary thyroid cancer. Differences in the level of IgG gamma expression between tumor size, between papillary thyroid cancer and normal thyroid tissue, as well as between papillary thyroid cancer with and without lymph node metastasis were significant. Taken together, these results indicate that IgG is produced by papillary thyroid cancer cells and that it might be positively related to the growth and metastasis of papillary thyroid cancer cells. Furthermore, it was demonstrated that IgG gamma colocalized with complement proteins in the same cancer cells, which could indicate that immune complexes were formed. Such immune complexes might consist of IgG synthesized by the host against tumor surface antigens and locally produced anti-idiotypic IgG with specificity for the variable region of these 'primary' antibodies. The cancer cells might thus escape the host tumor-antigen-specific immune responses, hence promoting tumor progression. Modern Pathology (2012) 25, 36-45; doi:10.1038/modpathol.2011.139; published online 9 September 2011