Immunoglobulin G expression in lung cancer and its effects on metastasis
Authors: Chunfan Jiang
Xia Wan
Yun Wang
Guowei Huang
Jiang Gu
Tao Huang
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: Lung cancer; immunoglobulin G; metastasis; squamous cell carcinomas; adenocarcinomas
Affiliations: 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., Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China; Translational Medicine Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, China.

Abstract:  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. 

Retracted: Yes

PubPeer comments:
 Please compare with  Differential effects of membrane and soluble Fas ligand on cardiomyocytes: role in ischemia reperfusion injury ([Date et al 2003] ). From the present text: *I. **Introduction** Fas or Fas ligand (FasL), a member of the tumor necrosis factor receptor superfamily, plays a central role in the regulation of apoptosis under various physio- logical and pathophysiological conditions [1]. Fas is expressed in all cell types examined, while physiological expression of FasL is found predominantly in activated T-lymphocytes, vascular endothelial cells, and u201cimmune-privilegedu201d tissues.* *Membrane FasL can be cleaved by metalloproteinases to produce a soluble form of FasL[1-3]. Soluble murine FasL loses the ability to induce apoptosis and inhibits membrane FasL- induced cytotoxicity, suggesting that the membrane FasL is the functional form. Although soluble human FasL retains low levels of biological activity in some biological settings, opposing effects of membrane and Shedding of membrane FasL provides a mechanism for down-regulating FasL Fas signaling[2-4]. The mode of FasL Fas interaction is also highly cell-type specific. apoptosis[5,6].* *In this study, We examined the relative importance of mitochondrial damage and direct cleavage of the executioner caspases by activated initiator caspase-8 in the propagation of FasL Fas signaling activated by either recombinant membrane FasL or simulated ischemia reperfusion.* ---------------------------------------------- From Date et al: *1. **Introduction** Fas, a death domain-containing member of the tumor necrosis factor receptor superfamily, plays a central role in the regulation of apoptosis under various physiological and pathophysiological conditions [1]. Fas is expressed in all cell types examined, while physiological expression of Fas ligand (FasL) is found predominantly in activated T-lymphocytes, vascular endothelial cells, and u201cimmune-privilegedu201d tissues. [...]* *Membrane FasL can be cleaved by metalloproteinases to produce a soluble form of FasL [1,6,7]. Soluble murine FasL loses the ability to induce apoptosis and inhibits membrane FasL-induced cytotoxicity, suggesting that the membrane FasL is the functional form. Although soluble human FasL retains low levels of biological activity in some biological settings, opposing effects of membrane and soluble FasL have been observed. Shedding of membrane FasL provides a mechanism for downregulating FasL Fas signaling [6u20138]. The mode of FasL Fas interaction is also highly cell-type specific. For example, antigen-activated apoptosis of T-cells may occur through soluble FasL-mediated suicide, in which a FasL expressing cell kills itself [9u201311]. In contrast, FasL Fas-mediated apoptosis in vascular smooth cells is likely to be u201cfratricidalu201d, in which cells expressing membrane FasL kill neighboring cells bearing Fas by apoptosis [12,13]. The mode of FasL Fas signaling in cardiomyocytes is not known.* [...] *In this study, we tested the hypothesis that shedding of membrane FasL is a mechanism for downregulating FasL Fas signaling and both membrane and soluble FasL contribute to ischemia reperfusion injury. We also examined the relative importance of mitochondrial damage and direct cleavage of the executioner caspases by activated initiator caspase 8 in the propagation of FasL Fas signaling activated by either recombinant membrane FasL or simulated ischemia reperfusion.* ,