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.

Highlights

  • Lung cancer is one of the leading malignant tumors worldwide with a very high mortality [1,2]

  • We further investigated the possible effects of cancer-produced immunoglobulin G (IgG) on cellular attachment and migration by using the technique of siRNA interference in an attachment assay, a transwell assay, and a wound healing assay with two lung cancer cell lines as well as a normal lung

  • We established the ability of lung cancer cells and related cell lines to express IgG gene

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Summary

Introduction

Lung cancer is one of the leading malignant tumors worldwide with a very high mortality [1,2]. By detecting IgG expression in 142 esophagus cancers and 80 soft tissue tumors, and comparative analysis of IgG expression with pathological parameters, cancerous IgG was found to correlate with tumor grade and proliferative markers such as PCNA and ki-67 in cancers of the breast, esophagus and soft tissues [8,11,29]. These results suggest that cancerous IgG might play a role in regulating cancer growth. The effect of IgG in lung cancer and the possible mechanism governing its actions have not been investigated

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