Immunoglobulin G expression in lung cancer and its effects on metastasis

PLoS One. 2014 May 22;9(5):e97359. doi: 10.1371/journal.pone.0097359. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / physiopathology*
  • Adenocarcinoma of Lung
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Line, Tumor
  • Cytidine Deaminase / metabolism
  • DNA Primers / genetics
  • DNA-Binding Proteins / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / physiology*
  • Histone Deacetylases / metabolism
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunoglobulin G / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Laser Capture Microdissection
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / physiopathology*
  • Lymph Nodes / pathology
  • Molecular Sequence Data
  • Neoplasm Metastasis / physiopathology*
  • Nuclear Proteins / metabolism
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / metabolism
  • Sequence Analysis, DNA
  • Trans-Activators

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin G
  • Mta1 protein, human
  • Nuclear Proteins
  • RAG2 protein, human
  • Repressor Proteins
  • Trans-Activators
  • RAG-1 protein
  • Histone Deacetylases
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase

Grant support

This work was supported by grants (30971150 to JG, 81001199 to ZC) from the National Natural Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.