Expression of immunoglobulins in human epithelial tumors and their potential role in carcinogenesis

Abstract

The traditional view of immunoglobulin (Ig) production only by B-lymphocytes and plasma cells has been revisited. Non-lymphoid tumor cells can also synthesize and secrete Ig with unidentified specificity. Expression of Ig genes was detected in the cells of malignant neoplasms of epithelial origin, such as breast carcinoma, colorectal cancer, prostate cancer, as well as in epithelial tumor cell lines. mRNA of the IgG1 heavy (H) chain constant region, sterile Iɣ-Cɣ transcript, H and light (L) chains of IgG, V(D)J recombination of H and L chain gene segments, as well as RAG1 (recombination-activating gene 1) and RAG2 enzymes, which are required for V(D)J recombination, were found in cancer cell lines and resected carcinoma tissues. IgG produced by cancer cells can be involved in the invasion and metastasis of these cells through interaction with E-cadherin, as well as with the metastasis-associated protein MTA1. Tumor-derived IgG plays an important role in malignant progression via activation of platelets by interacting with their FcγRIIa receptors and inducing the production of low levels of reactive oxygen species. The level of IgG in malignant neoplasms is positively correlated with proliferation markers, stage of progression, growth and survival of the tumor. These data modernize the current views on the mechanisms of carcinogenesis and create the basis for the search for new diagnostic and prognostic markers in malignant neoplasms, as well as methods of their target therapy. Further in-depth studies of the phenomenon of Ig production by tumor cells will contribute to more effective practical application of the accumulated knowledge in this field.