Jiang Chunfan, Huang Tao, Wang Yun, Huang Guowei, Wan Xia, Gu Jiang
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China; Department of pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China.
PLoS One. 2014 May 22;9(5):e97359. doi: 10.1371/journal.pone.0097359. eCollection 2014.
Lung cancer is one of the leading malignancies worldwide, but the regulatory mechanism of its growth and metastasis is still poorly understood. We investigated the possible expression of immunoglobulin G (IgG) genes in squamous cell carcinomas and adenocarcinomas of the lung and related cancer cell lines. Abundant mRNA of IgG and essential enzymes for IgG synthesis, recombination activation genes 1, 2 (RAG1, 2) and activation-induced cytidine deaminase (AID) were detected in the cancer cells but not in adjacent normal lung tissue or normal lung epithelial cell line. The extents of IgG expression in 86 lung cancers were found to associate with clinical stage, pathological grade and lymph node metastasis. We found that knockdown of IgG with siRNA resulted in decreases of cellular proliferation, migration and attachment for cultured lung cancer cells. Metastasis-associated gene 1 (MTA1) appeared to be co-expressed with IgG in lung cancer cells. Statistical analysis showed that the rate of IgG expression was significantly correlated to that of MTA1 and to lymph node metastases. Inhibition of MTA1 gene expression with siRNA also led to decreases of cellular migration and attachment for cultured lung cancer cells. These evidences suggested that inhibition of cancer migration and attachment induced by IgG down-regulation might be achieved through MTA1 regulatory pathway. Our findings suggest that lung cancer-produced IgG is likely to play an important role in cancer growth and metastasis with significant clinical implications.
肺癌是全球主要的恶性肿瘤之一,但其生长和转移的调控机制仍知之甚少。我们研究了免疫球蛋白G(IgG)基因在肺鳞状细胞癌和腺癌以及相关癌细胞系中的可能表达情况。在癌细胞中检测到了丰富的IgG mRNA以及IgG合成所需的关键酶、重组激活基因1、2(RAG1、2)和活化诱导的胞嘧啶脱氨酶(AID),但在邻近的正常肺组织或正常肺上皮细胞系中未检测到。发现86例肺癌中IgG的表达程度与临床分期、病理分级和淋巴结转移有关。我们发现用小干扰RNA(siRNA)敲低IgG会导致培养的肺癌细胞的细胞增殖、迁移和黏附能力下降。转移相关基因1(MTA1)似乎在肺癌细胞中与IgG共表达。统计分析表明,IgG的表达率与MTA1的表达率以及淋巴结转移显著相关。用siRNA抑制MTA1基因表达也会导致培养的肺癌细胞的细胞迁移和黏附能力下降。这些证据表明,通过MTA1调控途径可能实现抑制IgG下调诱导的癌症迁移和黏附。我们的研究结果表明,肺癌产生的IgG可能在癌症生长和转移中发挥重要作用,具有重要的临床意义。