Immunoglobulin G expression in carcinomas and cancer cell lines.
The traditional view that immunoglobulin is produced only by differentiated B lymphocytes has been challenged as immunoglobulin genes have been found to be expressed in nonhematopoietic human cancer cells. However, this phenomenon has not been widely accepted, and knowledge about this newly discovered concept is limited. In this study, we investigated the IgG1 heavy chain (IGHG1) constant region gene and IgG protein expression in 6 cell lines, including epithelial cancer cells, and in tissues from 66 hyperplasias, adenomas, and carcinomas. We also studied the mechanism of IgG production in these cells by examining the expression of RAG1 (recombination activating gene 1), RAG2, and AID (activation-induced cytidine deaminase). In cancer cell lines, mRNA of the IGHG1 constant region and Igamma-Cgamma sterile transcript were detected by nested RT-PCR, and Ig gamma and Ig kappa proteins were detected by immunofluorescence and Western blot. In surgically resected carcinoma tissues, we detected mRNA of the IGHG1 constant region by in situ hybridization, and by laser microdissection-assisted nested RT-PCR. Ig gamma and Ig kappa proteins were detected by immunohistochemistry. The V(D)J recombination of IgH and IgL loci, the Sgamma1/2-Smu switch circle, and the expression of RAG1 and RAG2 were also found in these cancer cell lines. These data suggest that cancer cells are capable of producing IgG. Because of its potential biological and clinical significance, this phenomenon warrants further investigation.
Chen
Zhengshan
Z
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Rd., Haidian District, Beijing 100083, China.
Gu
Jiang
J
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007834:Lasers; D042282:Microdissection; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015347:RNA Probes; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D015347:RNA Probes; C064658:RAG-1 protein