Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ recombinations by human epithelial cancer cells

Zheng, Hou-Feng; Li, Ming; Ren, Wei; Zeng, Liang; Liu, Haidan; Hu, Duosha; Deng, Xiyun; Tang, Min; Shi, Ying; Gong, Jianping; Cao, Yang

doi:10.1016/j.molimm.2006.11.010

Cited by 82 publications

(71 citation statements)

References 12 publications

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“…Flow cytometry analysis demonstrated that none of the cell lines were contaminated with B cells. 15 To explore the effects of the cancerous Ig heavy chain on HeLa human cervical cancer cell growth, we constructed an siRNA plasmid to silence the expression of all Ig heavy chain genes (psi-IgH). HeLa cells were stably transfected with this plasmid or a scrambled control plasmid to establish psi-IgH-HeLa cells or psi-scrambled-HeLa cells, which were used as a negative control.…”

Section: Resultsmentioning

confidence: 99%

Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines

Zheng

Zhi

et al. 2011

Cell Mol Immunol

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To explore the significance of cancerous immunoglobulin (Ig) in cancer cell growth, HeLa cervical cancer cells were stably transfected with small interfering RNA (siRNA) that specifically, efficiently and consistently silences the expression of heavy chain genes of all immunoglobulin isotypes. This stable cell line was used to examine cell viability, colony formation and tumor growth in athymic nude mice. The results of these experiments indicated that siRNA-mediated knockdown of cancerous Ig inhibited cell growth in vitro and suppressed tumor cell growth in immune-deficient nude mice in vivo. Similarly, this siRNA also inhibited the growth of MGC gastric cancer cells and MCF-7 breast cancer cells. Furthermore, the presence of cancerous Ig specifically reduced antibody-dependent cell-mediated cytotoxicity (ADCC) induced by an anti-human epithelial growth factor receptor (EGFR) antibody in a dose-dependent manner, suggesting that the cancerous Ig-Fc receptor interaction inhibits natural killer cell (or NK cell) effector function. The prevalent expression of Ig in human carcinomas and its capacity to promote growth and inhibit immunity might have important implications in growth regulation and targeted therapy for human cancers.

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Section: Resultsmentioning

confidence: 99%

Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines

Zheng

Zhi

et al. 2011

Cell Mol Immunol

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“…Although it was once presumed that B lymphocytes and plasma cells are the only sources of Ig, it has been recently reported that Ig is expressed in many types of neoplastic epithelial cells [1][2][3][4][5][6] and several types of non-hematopoietic cells from healthy individuals. [7][8][9] Moreover, non-hematopoietic cell-derived Ig shares some interesting features, including the restricted or biased usage of certain sequences, 9,10 a unique glycosylation profile 11,12 and novel regulatory mechanisms of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Rearrangement and expression of the immunoglobulin μ-chain gene in human myeloid cells

et al. 2013

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Immunoglobulin (Ig), a characteristic marker of B cells, has been reported to be expressed in epithelial cells, with a suggested role in their growth and survival. We have previously reported that IgG heavy chain is expressed in acute myeloid leukemia (AML), but not in the monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. In the present study, we assessed IgM heavy chain expression and repertoire in human myeloid cells. We detected V Hm DJ Hm rearrangement and expression in 7/7 AML cell lines, 7/14 primary myeloblasts from AML patients, and interestingly, 8/20 monocytes and 3/20 neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. We also found evidence of somatic hypermutation of the variable (V) gene segments in AML-derived IgM gene rearrangements but not in IgM from monocytes or neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. Furthermore, IgM V Hm DJ Hm gene rearrangements in AML cell lines, primary myeloblasts, and monocytes and neutrophils from patients with non-hematopoietic neoplasms showed a restricted V usage and repertoire, whereas the V Hm DJ Hm gene rearrangements in monocytes and neutrophils from healthy individuals displayed more diversity. Anti-human IgM inhibited cell proliferation, but did not induce apoptosis in AML cell lines. Our findings suggest that AML-derived IgM might be a novel AML-related molecule that is involved in leukemogenesis and AML progression and might serve as a useful molecular marker for designing targeted therapy and monitoring minimal residual disease.

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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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Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ recombinations by human epithelial cancer cells

Cited by 82 publications

References 12 publications

Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines

Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines

Rearrangement and expression of the immunoglobulin μ-chain gene in human myeloid cells

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

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