Heterogeneity of aberrant immunoglobulin expression in cancer cells

Hu, Duosha; Zhi, Deng; Li, Ming; Jiang, Yiqun; Liu, Haidan; Zheng, Hou-Feng; Li, Lili; Bode, Ann M.; Dong, Zigang; Cao, Yang

doi:10.1038/cmi.2011.25

Cited by 33 publications

(22 citation statements)

References 29 publications

(33 reference statements)

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“…This phenomenon can only be explained based on the fact that atypical cancerous immunoglobulins are aberrantly glycosylated, resulting in significant alternations in protein structures and immunoactivities of the former. This observation was consistent with an earlier report by other scientists regarding the heterogeneity arising from aberrant immunoglobulin expression in cancer cells (Hu et al, 2011). (Lee and Ge, 2009) with permission.…”

Section: Normal Immunoglobulinssupporting

confidence: 82%

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: Normal Immunoglobulinssupporting

confidence: 82%

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Lee

2012

American Journal of Immunology

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“…Immunoglobulins expressed by cancer cells were initially reported more than a decade ago [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. By use of nested reverse transcription polymerase chain reaction (RT-PCR) on a single cell, it was first observed that the genes of antigen receptors, including those of immunoglobulins and T cell receptors (TCRs), were expressed among several different cancer cell lines [1,3,5,6,13].…”

Section: Introductionmentioning

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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“…Our previous studies have demonstrated that CNE1 and HeLa cells can produce and secrete Igs spontaneously. 18,28 The Burkitt's lymphoma cell line Raji (ATCC number: CCL-86) was used as a positive control for expression of the Iga heavy chain. All the cell lines were cultured in complete growth medium according to ATCC protocols, and logarithmically growing cells were used in all experiments.…”

Section: Methodsmentioning

confidence: 99%

Activation of the Ig Iα1 promoter by the transcription factor Ets-1 triggers Ig Iα1–Cα1 germline transcription in epithelial cancer cells

Zhi

Zheng

et al. 2013

Cell Mol Immunol

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Immunoglobulins (Igs) are known to be synthesized and secreted only by B lymphocytes. Class switch recombination (CSR) is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Ig genes. Surprisingly, recent studies have demonstrated that the Ig genes are also expressed in some epithelial cancer cells; however, the mechanisms underlying how cancer cells initiate CSR and express Igs are still unknown. In this study, we confirmed that the Ig Ia1 promoter in cancer cell lines was activated by the Ets-1 transcription factor, and the activity of the Ig Ia1 promoter and Ig Ia1-Ca1 germline transcription were attenuated after knockdown of Ets-1 by specific small interfering RNAs (siRNA). Furthermore, the expression of Ets-1 and Iga heavy chain in cancer cells was dose dependently upregulated by TGF-b1. These results indicate that activation of the Ig Ia1 promoter by the transcription factor Ets-1 is a critical pathway and provides a novel mechanism for Ig expression in non-B cell cancers.

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Heterogeneity of aberrant immunoglobulin expression in cancer cells

Cited by 33 publications

References 29 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

Activation of the Ig Iα1 promoter by the transcription factor Ets-1 triggers Ig Iα1–Cα1 germline transcription in epithelial cancer cells

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