Immunoglobulin alpha heavy chain derived from human epithelial cancer cells promotes the access of S phase and growth of cancer cells

Zheng, Hou-Feng; Li, Ming; Liu, Haidan; Ren, Wei; Hu, Duosha; Shi, Ying; Tang, Ming; Cao, Yang

doi:10.1016/j.cellbi.2006.09.009

Cited by 52 publications

(46 citation statements)

References 14 publications

(22 reference statements)

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“…2 Zheng et al reported that blockade of cancer-derived Iga suppressed the growth and viability of cancer cells. 18 In the current study, we observed that Ig expression had a positive association with tumor proliferation activity, a finding that was consistent with the hypothesis that Ig promotes tumor growth and proliferation. Many studies have evaluated the relation between proliferation markers and clinical outcome in patients with sarcoma.…”

Section: Discussionsupporting

confidence: 91%

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

Chen

Huang²,

et al. 2010

Cancer

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BACKGROUND:The traditional view that immunoglobulin (Ig) is produced only by B lymphocytes has been challenged, because it has been demonstrated that Ig genes and proteins are expressed in epithelial cancer cells. However, whether Ig expression in nonlymphoid cells is limited to epithelial cells is unclear. Because sarcomas differ distinctly from carcinomas in their biologic and clinical features, the authors investigated the question of nonlymphoid IgG expression in soft tissue lesions. METHODS: Immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR) were used to demonstrate IgG expression in 80 soft tissue lesions. The correlation between Ig expression and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki-67, and cyclin D1) in sarcomas was investigated by immunohistochemical and statistical analyses. RESULTS: Igj was identified in 97.4% of sarcomas and in 31.7% of benign lesions by immunohistochemistry. The difference was statistically significant (P < .01). Messenger RNA from the IgG1 heavy-chain constant region was also detected by in situ hybridization. Variable-diversity-joining recombination sequences of both heavy and light chains were obtained by PCR and sequencing. Moreover, the labeling index of PCNA, Ki-67, and cyclin D1 was much higher in sarcomas with high Igj expression than in sarcomas with low Igj expression (P < .01 for PCNA and cyclin D1; P < .001 for Ki-67). There were more grade 3 sarcomas with high Igj expression compared with grade 1 and 2 sarcomas (P < .05). CONCLUSIONS: IgG was identified in a wide variety of soft tissue tumors and correlated well with proliferation markers and tumor grades. IgG may be a useful marker for cell proliferation in sarcomas.

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Section: Discussionsupporting

confidence: 91%

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

Chen

Huang²,

et al. 2010

Cancer

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“…[3][4][5][6][7][8][9][10] In our previous studies addressing the significance of cancerous Ig expression, we found that depletion of tumor-derived Ig by either antisense RNA or a human IgG or IgA antibody resulted in an increase in apoptosis and inhibition of cancer cell growth in vitro and in vivo. 3,11 Moreover, we extended our findings by using in situ hybridization to detect Ig kappa light chain expression in clinical cervical tissue samples, including cervicitis, dysplasia and cancer samples. In these experiments, we detected a remarkable increase in Ig kappa light chain expression that paralleled the escalating severity of epithelial transformation.…”

Section: Introductionmentioning

confidence: 61%

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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“…Our recent studies showed that the level of the cancerous Ig k light chain could be upregulated by the exogenous oncoprotein, latent membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus in nasopharyngeal carcinoma (NPC) and triggers several signal pathways mediated through nuclear factor-kappa B (NF-KB) and activator protein-1 (AP-1). 19,20 Our findings indicated that cancerous Ig plays a potential role in the process of cell transformation. Overall, cancerous Ig is different from normal Ig.…”

Section: Introductionmentioning

confidence: 65%

“…19 Immunofluorescence Cells were fixed and stained using a standard immunofluorescence protocol (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA). The following antibodies were used: Alexa Fluor 488-labeled Table 1 The common features and differences between Ig produced by cancer cells and Ig produced by B cells …”

Section: Western Blot Analysismentioning

confidence: 99%

Heterogeneity of aberrant immunoglobulin expression in cancer cells

Zhi

et al. 2011

Cell Mol Immunol

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Accumulating evidence has shown that immunoglobulin (Ig) is 'unexpectedly' expressed by epithelial cancer cells and that it can promote tumor growth. The main purpose of this study was to explore the components of the cancerous Ig and its possible function. The presence of cancerous Ig in the Golgi apparatus was confirmed by immunofluorescence, indirectly suggesting that the cancerous Ig was processed and packaged in cancer cells. Western blot analysis and ELISA results indicated that cancer cells produced membrane Ig and secreted Ig into the supernatant fraction. The cancerous Ig consists of an a heavy chain and a k light chain. Finally, by analyzing the Ig components pulled down by protein A beads, the cancerous Ig was found to be structurally distinct from normal Ig. The cancerous Ig was truncated or aberrant. Although the underlying mechanism that causes the abnormalities has not been determined, our current discoveries strengthen our previous findings and promise fruitful future explorations.

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Immunoglobulin alpha heavy chain derived from human epithelial cancer cells promotes the access of S phase and growth of cancer cells

Cited by 52 publications

References 14 publications

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

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

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

Heterogeneity of aberrant immunoglobulin expression in cancer cells

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