Fucosyl-agalactosyl IgG 1 induces cholangiocarcinoma metastasis and early recurrence by activating tumor-associated macrophage

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Abstract

Concern over roles of serum IgG agalactosylation in chronic inflammatory diseases has been mounting for years but less touched in cancers. The present study addressed the underlying role of agalactosylated IgG beyond tumorigenesis. Liquid-chromatography-tandem mass spectrometry was leveraged for the analysis of IgG 1 and IgG 2 N-glycomes. We found that a high percentage of serum fucosyl-agalactosyl IgG 1 (IgG 1 -G0F) in patients with cholangiocarcinoma was associated with poor tumor differentiation and tumor metastasis. Results from Kaplan–Meier analyses and a stepwise Cox regression analysis showed that patients with serum IgG 1 -G0F ≥40% were highly correlated with poor recurrence-free survivals and overall survivals. Interestingly, patients with cholangiocarcinoma whose serum IgG 1 -G0F ≥40% had more CD163+ tumor-associated macrophages in cancerous tissues than adjacent non-cancerous counterparts. In vitro assays revealed that agalactosylated IgG upregulated tumor-associated macrophage markers CD163 and CD204 in human U-937 cells and peripheral macrophages. Moreover, a positive and a negative feedback loop of transforming growth factor-β1 and interferon-γ, respectively, on IgG agalactosylation was identified using hybridoma cells and verified in sera of the patients. In conclusion, agalactosylated IgG activates tumor-associated macrophages, thereby promoting tumor metastasis and recurrence of cholangiocarcinoma.

Original languageEnglish
Article number460
JournalCancers
Volume10
Issue number11
DOIs
Publication statusPublished - 2018 Nov 21

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Cholangiocarcinoma
Immunoglobulin G
Macrophages
Neoplasm Metastasis
Recurrence
Neoplasms
Serum
Survival
Hybridomas
Transforming Growth Factors
Tandem Mass Spectrometry
Liquid Chromatography
Interferons
Carcinogenesis
Chronic Disease
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Fucosyl-agalactosyl IgG 1 induces cholangiocarcinoma metastasis and early recurrence by activating tumor-associated macrophage",
abstract = "Concern over roles of serum IgG agalactosylation in chronic inflammatory diseases has been mounting for years but less touched in cancers. The present study addressed the underlying role of agalactosylated IgG beyond tumorigenesis. Liquid-chromatography-tandem mass spectrometry was leveraged for the analysis of IgG 1 and IgG 2 N-glycomes. We found that a high percentage of serum fucosyl-agalactosyl IgG 1 (IgG 1 -G0F) in patients with cholangiocarcinoma was associated with poor tumor differentiation and tumor metastasis. Results from Kaplan–Meier analyses and a stepwise Cox regression analysis showed that patients with serum IgG 1 -G0F ≥40{\%} were highly correlated with poor recurrence-free survivals and overall survivals. Interestingly, patients with cholangiocarcinoma whose serum IgG 1 -G0F ≥40{\%} had more CD163+ tumor-associated macrophages in cancerous tissues than adjacent non-cancerous counterparts. In vitro assays revealed that agalactosylated IgG upregulated tumor-associated macrophage markers CD163 and CD204 in human U-937 cells and peripheral macrophages. Moreover, a positive and a negative feedback loop of transforming growth factor-β1 and interferon-γ, respectively, on IgG agalactosylation was identified using hybridoma cells and verified in sera of the patients. In conclusion, agalactosylated IgG activates tumor-associated macrophages, thereby promoting tumor metastasis and recurrence of cholangiocarcinoma.",
author = "Ting-Tsung Chang and Hung-Wen Tsai and Ho, {Cheng Hsun}",
year = "2018",
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language = "English",
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T1 - Fucosyl-agalactosyl IgG 1 induces cholangiocarcinoma metastasis and early recurrence by activating tumor-associated macrophage

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AU - Ho, Cheng Hsun

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AB - Concern over roles of serum IgG agalactosylation in chronic inflammatory diseases has been mounting for years but less touched in cancers. The present study addressed the underlying role of agalactosylated IgG beyond tumorigenesis. Liquid-chromatography-tandem mass spectrometry was leveraged for the analysis of IgG 1 and IgG 2 N-glycomes. We found that a high percentage of serum fucosyl-agalactosyl IgG 1 (IgG 1 -G0F) in patients with cholangiocarcinoma was associated with poor tumor differentiation and tumor metastasis. Results from Kaplan–Meier analyses and a stepwise Cox regression analysis showed that patients with serum IgG 1 -G0F ≥40% were highly correlated with poor recurrence-free survivals and overall survivals. Interestingly, patients with cholangiocarcinoma whose serum IgG 1 -G0F ≥40% had more CD163+ tumor-associated macrophages in cancerous tissues than adjacent non-cancerous counterparts. In vitro assays revealed that agalactosylated IgG upregulated tumor-associated macrophage markers CD163 and CD204 in human U-937 cells and peripheral macrophages. Moreover, a positive and a negative feedback loop of transforming growth factor-β1 and interferon-γ, respectively, on IgG agalactosylation was identified using hybridoma cells and verified in sera of the patients. In conclusion, agalactosylated IgG activates tumor-associated macrophages, thereby promoting tumor metastasis and recurrence of cholangiocarcinoma.

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