Immunoglobulin G Expression and its Potential Role in Primary and Metastatic Breast Cancers

Abstract

Recently immunoglobulin G (IgG) was found to be produced by neoplasms and promote tumor growth in cancer cell lines and animal models. To investigate the pathophysiological significance of cancer-produced IgG in breast cancer, we examined the expressions of IgG in 68 breast cancers including 40 primary cancers without metastasis and 28 cancers with axillary lymph node metastases. IgG gene expression was detected in all these samples. We found that IgG-expressing cancer cells were predominantly located in the periphery of the primary cancer nest and that these cells showed more cellular atypia and nuclear pleomorphism. We also found that the abundance of IgG-expressing cancer cells was higher and the cells were more evenly distributed in the metastatic cancer cells than that in the primary lesion. These findings suggest that IgG-expressing breast cancer cells have a more aggressive biological behavior than the IgG negative cancer cells and it could be an indicator for progression and metastasis of the disease. Co-localization of IgG and C1q complement was detected in both primary and metastatic lesions implying that immune complexes might be formed in situ. We speculate that such immune complexes might facilitate immune escape of cancer cells. Our findings suggest that locally produced IgG plays important roles in breast cancer, and may serve as a potential therapeutic target.

Immunoglobulin G Expression in Lung Cancer and Its Effects on Metastasis

“…We also found that lung cancers with lymph node metastasis had higher expression rate of IgG. Similar observations were made by Ma et al in breast cancers [29]. These observations suggest that IgG producing cancer cells may have disordered cell cycles and chromatin replication.…”

“…Blockade of cancerous IgG with antisense RNA or IgG antibody suppressed cancer cell growth and increased apoptosis [5], [26]–[28]. 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.…”

Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation through inducing production of reactive oxygen species

“…These include cancer cells such as breast cancer cells, 1, 2, 3 colorectal cancer cells, 4, 5 prostate cancers cells, 6 papillary thyroid cancer cells 7 and soft tissue tumors, 8 human umbilical endothelial cells, 9 testicular spermatogenic cells, 10 epididymal epithelial cells, 10 human and mouse neurons 11, 12 and eyes. 13 It was reported that IgG secreted by human cancers promoted growth and survival of tumor cells.…”

“…1 IgG detected in a wide variety of neoplasms was found to correlate with proliferation markers and tumor grades. 1, 3, 5 Furthermore, knockdown of the expression of heavy-chain genes of immunoglobulin isotypes through siRNA suppressed cancer cell growth in vitro and in vivo . 14 However, the regulatory mechanism of the above biological effects remains uncertain.…”

CA215, A New Pan Cancer Biomarker, and its Clinical Applications

“…Since CA215 is cancer-associated, elevated levels of CA215 in the human circulation may indicate active growth/proliferation or metastasis of cancer cells in the human body [1,2,5,11,[13][14][15][16][17][18][19][20]. Immunoassays using RP215 as a unique substitute for antibodies against cancerous immunoglobulins have been established for the quantitative determination of serum levels of CA215 [1].…”