Regulation of cytokine production in carcinoembryonic antigen stimulated Kupffer cells by β-2 adrenergic receptors: implications for hepatic metastasis

Thomas, Peter; Hayashi, Hiroshi; Zimmer, Regis; Forse, R. Armour

doi:10.1016/j.canlet.2003.12.027

Cited by 28 publications

(17 citation statements)

References 21 publications

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“…This results in increased levels of IL-10 and a decrease in TNF-a production. Exposure of Kupffer cells to CEA also causes an up-regulation of the b-adrenergic receptor mRNA, as well as changes in the cytokine responses mentioned above [102]. Interestingly Blaxall et al also showed interactions between the b-adrenergic receptor and members of the hnRNP family of proteins including hnRNP A [109].…”

Section: Cea and Liver Metastasismentioning

confidence: 92%

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Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver

Thomas

Forse

Bajenova

2011

Clin Exp Metastasis

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This article discusses the role of carcinoembryonic antigen (CEA) as a facilitator of the inflammatory response and its effect on colorectal cancer hepatic metastasis. Colorectal cancer accounts for 11% of all cancers in the United States and the majority of deaths are associated with liver metastasis. If left untreated, median survival is only six to 12 months. Resection of liver metastases offers the only chance for cure. Of the small number of patients who have operable cancer most will have further tumor recurrence. The molecular mechanisms associated with colorectal cancer metastasis to the liver are largely unknown. However CEA production has been shown both clinically and experimentally to be a factor in an increased metastatic potential of colorectal cancers to the liver. CEA also has a role in protecting tumor cells from the effects of anoikis and this affords a selective advantage for tumor cell survival in the circulation. CEA acts in the liver through its interaction with its receptor (CEAR), a protein that is related to the hnRNP M family of RNA binding proteins. In the liver CEA binds with hnRNP M on Kupffer cells and causes activation and production of pro- and anti-inflammatory cytokines including IL-1, IL-10, IL-6 and TNF-α. These cytokines affect the up-regulation of adhesion molecules on the hepatic sinusoidal endothelium and protect the tumor cells against cytotoxicity by nitric oxide (NO) and other reactive oxygen radicals. HnRNP M signaling in Kupffer cells appears to be controlled by beta-adrenergic receptor activation. The cells will respond to the β-adrenergic receptor agonist terbutaline resulting in reduced TNF-α and increased IL-10 and IL-6 production following CEA activation. This has implications for the control of tumor cell implantation and survival in the liver.

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Section: Cea and Liver Metastasismentioning

confidence: 92%

“…The activation of Kupffer cells by CEA is also affected by the b-adrenergic receptor agonist terbutaline [102]. Indeed the response of macrophages to many outside stimuli is regulated by b-adrenergic signals [103][104][105].…”

Section: Cea and Liver Metastasismentioning

confidence: 99%

Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver

Thomas

Forse

Bajenova

2011

Clin Exp Metastasis

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“…When CEA is complexed, KCs are activated and secrete through β-2 adrenergic pathways large amounts of cytokines, including TNF-α, IL-1β, IL-6 and IL-10 [141,143] . These pro-and anti-inflammatory agents generate alterations in the sinusoidal endothelium and SECs express adhesion molecules of the selectin family, which promote the arrest and extravasation of tumour cells [144] .…”

Section: Kupffer Cellsmentioning

confidence: 99%

“…KCs present an 80 kDa carcinoembryonic antigen (CEA) receptor, which mediates binding and subsequent degradation of CEA [141,142] . When CEA is complexed, KCs are activated and secrete through β-2 adrenergic pathways large amounts of cytokines, including TNF-α, IL-1β, IL-6 and IL-10 [141,143] .…”

Section: Kupffer Cellsmentioning

confidence: 99%

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Paschos

Majeed

Bird

2014

WJG

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Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. Paschos KA, Majeed AW, Bird NC. Natural history of hepatic metastases from colorectal cancer -pathobiological pathways with clinical significance.

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“…CEA is measured in the blood plasma. It is very nonspecific and can be increased in many types of cancer: gastrointestinal, colorectal, ovarian, bladder, cervical, stomach, kidney, lung, pancreatic, liver, prostate, thyroid, melanoma, lymphoma, and breast [3]. People with noncancerous conditions, such as cirrhosis or peptic disease, or inflammatory intestinal conditions such as colitis or diverticulitis, may also have increased levels [4].…”

Section: Introductionmentioning

confidence: 95%

Electroanalytical Determination of Carcinoembryonic Antigen at a Silica Nanoparticles/Titania Sol–Gel Composite Membrane‐Modified Gold Electrode

Liu¹,

Jiang²

2006

Electroanalysis

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A highly hydrophilic and nontoxic colloidal silica nanoparticle/titania sol -gel composite membrane was prepared on a gold electrode via a chemical vapor deposition method. With carcinoembryonic antigen (CEA) as a model antigen and encapsulation of carcinoembryonic antibody (anti-CEA) in the composite architecture, this membrane could be used for reagentless electrochemical immunoassay. The presence of silica nanoparticles provided a congenial microenvironment for adsorbed biomolecules. The formation of immunoconjugate by a simple one-step immunoreaction between CEA in sample solution and the immobilized anti-CEA introduced the change in the potential. The modified procedure was further characterized by electrochemical impedance spectroscopy and cyclic voltammetry. Compared to the commonly applied methods, i.e., the TiO 2 direct embedding procedure, this strategy could allow for antibodies immobilized with higher loading amount and better retained immunoactivity. The resulting immunosensor exhibited high sensitivity, good precision, acceptable stability, accuracy, reproducibility and wide linear range from 1.5 to 240 ng mL À1 with a detection limit of 0.5 ng mL À1 at 3s. Analytical results of clinical samples show that the developed immunoassay is comparable with the enzyme-linked immunosorbent assays (ELISAs) method, implying a promising alternative approach for detecting CEA in the clinical diagnosis. Furthermore, this composite membrane could be used efficiently for the entrapment of other biomarkers and clinical applications.

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Regulation of cytokine production in carcinoembryonic antigen stimulated Kupffer cells by β-2 adrenergic receptors: implications for hepatic metastasis

Cited by 28 publications

References 21 publications

Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver

Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Electroanalytical Determination of Carcinoembryonic Antigen at a Silica Nanoparticles/Titania Sol–Gel Composite Membrane‐Modified Gold Electrode

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