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

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

doi:10.1038/cmi.2011.40

Cited by 65 publications

(67 citation statements)

References 14 publications

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“…15,23 Li et al found that cancerous immunoglobulin promoted cell proliferation and inhibited antibody-dependent cell-mediated cytotoxicity. 26 It is possible that hepatocyte-produced IgG acts as a growth factor to participate in signaling pathways, leading to cell proliferation and apoptosis in normal hepatocytes and hepatocarcinomas. Therefore, hepatocyte-produced Ig may also affect liver transplant, regeneration and repair.…”

Section: Discussionmentioning

confidence: 99%

Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver

Huang

et al. 2014

Laboratory Investigation

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The liver has the extraordinary properties of regeneration and immune tolerance; however, the mechanisms governing these abilities are poorly understood. To address these questions, we examined the possible expression of immunoglobulins in the human and rat liver and the relationship of IgG expression to hepatocyte proliferation, metastasis, apoptosis and immune tolerance. Immunohistochemistry, in situ hybridization, laser-guided microdissection and reverse transcription-PCR were performed to examine the expression of IgG in normal human and rat liver, severe combined immunodeficient mouse (SCID) liver and human liver cancers and corresponding cell lines. Small interfering RNA (siRNA) was transfected into cultured hepatocarcinoma cells to downregulate the expression of IgG heavy chain genes. Cell proliferation and apoptosis were assayed with flow cytometry. Cell metastasis was assayed with a Transwell cell assay. Partial hepatectomy (70%) was performed in rats to examine the relationship between hepatocyte IgG and hepatocyte proliferation. IgG, together with essential enzymes for its synthesis, were expressed in the cytoplasm of hepatocytes of normal adult human and hepatoma patients and rat livers, SCID mouse liver and BRL-3A, L-02 and HepG-2 cell lines. Downregulation of IgG inhibited cell proliferation and metastasis and promoted apoptosis. Postsurgery livers expressed significantly more IgG than the livers before surgery and decreased to the original levels when hepatocytes stopped regeneration. IgA and IgM but not IgD and IgE were also positive in hepatocytes. Our findings demonstrate that normal and malignant hepatocytes are capable of synthesizing immunoglobulin, which has important roles in hepatocyte proliferation, apoptosis and cancer growth with profound clinical implications.

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Section: Discussionmentioning

confidence: 99%

Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver

Huang

et al. 2014

Laboratory Investigation

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“…13,14 Furthermore, non-hematopoietic cellderived Ig has a role in cell growth and survival. 1,3,15,16 These findings suggest that Ig derived from non-hematopoietic cells might be a novel molecule with a unique structure and function and might play a role in carcinogenesis and/or tumor progression.…”

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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“…Among the serum proteins or fragments detected by LC-MS/MS, more than half were found to be relevant to the growth/proliferation or inhibition of cancer cells in vitro or in vivo, as demonstrated by other researchers (M. Li et al, 2004;M. Li et al, 2012;Qiu et al, 2003).…”

Section: Biochemical and Immunological Characterizations Of Ca215-s+mentioning

confidence: 74%

“…Previous studies have indicated that through binding to the RP215-specific epitope in CA215 on the surface of cultured cancer cells, apoptosis was induced as judged by using the TUNEL assay method (Chen & Gu, 2007;Lee et al, 2010;Lee & Ge, 2010;Lee, Cheung, Ge, et al, 2012;M. Li et al, 2012;Qiu et al, 2003;.…”

Section: Apoptosis Experimentsmentioning

confidence: 99%

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Human Serum Proteins Recognized by CA215 and Cancerous Immunoglobulins and Implications in Cancer Immunology

Lee¹,

Liu²,

Huang³

2014

CCO

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In 1987, a monoclonal antibody, RP215, was generated against the OC-3-VGH cancer cell line and shown to react with a carbohydrate-associated epitope located mainly on the heavy chains of immunoglobulins, designated as CA215, which are expressed on the surface of almost all cancer cells and not on normal immune cells. CA215 and cancerous immunoglobulins were affinity-isolated from the shed culture media of the same ovarian cancer cell line by using RP215-linked and anti-human immunoglobulin G-linked affinity chromatography, respectively. They were then immobilized separately as general ligands to isolate any protein components from pooled human sera which demonstrated affinity to CA215 and/or cancerous immunoglobulin G. The affinity-isolated components were then subjected to molecular analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the detected protein components, more than 72% were found to be commonly recognized by both CA215 and cancerous immunoglobulins. Some have previously been identified as endogenous proteins or fragments in human serum. They are considered generally, as cancer biomarkers, according to their pro-cancer (e.g. C4b binding protein α chain, complement C3, complement factor H, serotransferrin, and vironectin), anti-cancer (e.g. 35 kDa inter-α-trypsin inhibition heavy chain 4, anastellin, apolipoprotein A-1, fibrinogen β chain, and, keratin type I cytoskeletal 9), or autoimmune (specific immunoglobulin G) properties, respectively. Therefore, besides serving a role for the growth/proliferation of cancer cells, cancerous immunoglobulins can also interact directly or indirectly with many other serum protein components or fragments for unspecified reasons and unknown mechanisms of action.

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

Cited by 65 publications

References 14 publications

Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver

Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver

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

Human Serum Proteins Recognized by CA215 and Cancerous Immunoglobulins and Implications in Cancer Immunology

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