Immunoglobulin G is present in a wide variety of soft tissue tumors and correlates well with proliferation markers and tumor grades

Chen, Zhengshan; Huang, Xinrui; Ye, Juxiang; Pan, Peng; Cao, Qi; Yang, Baokai; Li, Zhuo; Su, Meng; Huang, Can; Gu, Jiang

doi:10.1002/cncr.24892

Cited by 56 publications

(55 citation statements)

References 35 publications

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“…Besides cancer cells of epithelial cell origins, the majority of soft tissue tumors (Chen et al, 2010;Liu et al, 2012;Qiu et al, 2012b), such as sarcomas, were also found to express immunoglobulins, with the level of these atypical immunoglobulins correlating with markers of proliferation (PCNA, KI67, cyclin D1) and tumor grades (Zhang et al, 2012). Based on the results of this study, it was concluded that the expression of atypical immunoglobulins was a common characteristic of all human cancers (Chen et al, 2009;Hu et al, 2008;Kimoto, 1998;Lee and Ge, 2009).…”

Section: Expression Of Immunoglobulins By Normal and Cancer Cells Inmentioning

confidence: 59%

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Lee

2012

American Journal of Immunology

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Immunoglobulins are typically expressed by B cells in our normal immune system. However, certain normal human tissues, such as hyperplastic epithelial cells, cells of the immunologically privileged sites and the majority of cancer cells, have also been found to be sites of immunoglobulin production. Current research is lacking in regards to the differential immunoglobulin expression, the underling mechanisms of action and the biological implications of these cancerous immunoglobulins in cancer immunology. This article reviews the etiology of atypical immunoglobulin expression in normal non-B cells and cancer cells, with emphasis on the exploration of the possible mechanisms of action and biological function of these atypical immunoglobulins, by means of specific biological probes. In contrast to immunoglobulins of B cell origins, atypical immunoglobulins were found to carry additional post-translational modifications, including a unique carbohydrateassociated epitope recognized by RP215 monoclonal antibody. This unique RP215-specific epitope enables us to differentiate between these two types of immunoglobulins. Atypical immunoglobulins expressed by cancer cells have been a common subject of interest in cancer immunology. Furthermore, the recent accumulation of experimental evidence has indicated that these atypical immunoglobulins are essential for the growth and proliferation of cancer cells under our normal immune environment. RP215 monoclonal antibody also reacts with many other cancer cell-expressed glycoproteins, known as CA215, on the cancer cell surface. Apoptosis of cultured cancer cells can be induced and growth inhibition of implanted tumors can be observed in nude mouse animal models. Therefore, humanized RP215 monoclonal antibody, which reacts mainly with surface bound CA215, may have the potential to be developed as an anti-cancer drug for the treatment of human cancers. A better understanding of cancer cell-expressed immunoglobulins not only improves our knowledge of cancer immunology, but also benefits cancer patients in the field of cancer monitoring and therapeutic treatments.

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Section: Expression Of Immunoglobulins By Normal and Cancer Cells Inmentioning

confidence: 59%

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Lee

2012

American Journal of Immunology

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“…Most of the non-B cell-expressed immunoglobulins were found in tissues containing hyperplastic epithelial cells, including those of the skin, esophagus, cervix, and immune privileged sites, such as in the eyes, testis, brain neuron, and placenta [31]. Due to the lack of experimental evidence, the immunoglobulin expressions among these normal tissues could only be explained by the assumption that they may be required for immune protection [17,27,[33][34][35][36][37][38][39].…”

Section: Expressions Of Immunoglobulins and Ca215 From Non-b Cellsmentioning

confidence: 99%

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

Lee¹,

Liu²

2013

OJI

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Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that cancerous immunoglobulins play significant roles in the growth and proliferation of cancer cells in vitro and in vivo. RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. Through gene regulation studies, both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell proliferation (such as NFκB-1, IgG, P21, cyclin D1, ribosomal P 1 , and c-fos). Furthermore, selected toll-like receptor genes (TLR-2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and antiantigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and downregulate TLR-4 and TLR-9 in two types of cancer cells. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins play important roles in the modulation of the innate immune system to allow the growth and survival of cancer cells within the human body. Consequently, RP215 in its humanized forms may be utilized to target cancer cells for potential therapeutic purposes.

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“…[2][3][4][5] IgG expression has also been found in colon carcinoma, breast carcinoma, lung carcinoma, and soft tissue tumors. [6][7][8][9] The exact function of IgG in cancers has not yet been elucidated, but IgG might be involved in the promotion of tumor growth based on preliminary in vitro evidence of its capacity to stimulate cell proliferation and invasion. 6,10 Another observation supporting a growth-promoting role of IgG include the observed correlation between the level of IgG expression and tumor grade and stage in soft tissue tumors.…”

mentioning

confidence: 99%

“…6,10 Another observation supporting a growth-promoting role of IgG include the observed correlation between the level of IgG expression and tumor grade and stage in soft tissue tumors. 9 To date, it is not known whether papillary thyroid cancer cells also produce IgG. Lucas et al, 11 detected cellular deposits of IgG in 80% of 41 papillary thyroid cancer cases studied.…”

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confidence: 99%

Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer

et al. 2012

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Except for the well-known immunoglobulin G (IgG) producing cell types, ie, mature B lymphocytes and plasma cells, various non-lymphoid cell types, including human cancer cells, neurons, and some specified epithelial cells, have been found to express IgG. In this study, we detected the expression of the heavy chain of IgG (IgGc) and kappa light chain (Igj) in papillary thyroid cancer cells. Using in situ hybridization, we detected the constant region of human IgG1 (IGHG1) in papillary thyroid cancer cells. With laser capture microdissection followed by RT-PCR, mRNA transcripts of IGHG1, Igj, recombination activating gene 1 (RAG1), RAG2, and activation-induced cytidine deaminase genes were successfully amplified from isolated papillary thyroid cancer cells. We further confirmed IgG protein expression with immunohistochemistry and found that none of the IgG receptors was expressed in papillary thyroid cancer. Differences in the level of IgGc expression between tumor size, between papillary thyroid cancer and normal thyroid tissue, as well as between papillary thyroid cancer with and without lymph node metastasis were significant. Taken together, these results indicate that IgG is produced by papillary thyroid cancer cells and that it might be positively related to the growth and metastasis of papillary thyroid cancer cells. Furthermore, it was demonstrated that IgGc colocalized with complement proteins in the same cancer cells, which could indicate that immune complexes were formed. Such immune complexes might consist of IgG synthesized by the host against tumor surface antigens and locally produced anti-idiotypic IgG with specificity for the variable region of these 'primary' antibodies. The cancer cells might thus escape the host tumor-antigen-specific immune responses, hence promoting tumor progression.

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Immunoglobulin G is present in a wide variety of soft tissue tumors and correlates well with proliferation markers and tumor grades

Cited by 56 publications

References 35 publications

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer

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