Carcinoembryonic antigen induces signal transduction in Kupffer cells

Gangopadhyay, Aniruddha; Lazure, Donald A.; Thomas, Peter

doi:10.1016/s0304-3835(97)00216-4

Cited by 23 publications

(12 citation statements)

References 13 publications

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“…35 The tumor-specific patterns of cytokine and CAM induction that we observed most likely reflects the distinct repertoires of cytokines/chemokines produced by the tumor cells or, for the human colorectal carcinoma lines, a differential ability to produce carcinoembryonic antigen. 43 Indeed, we have recently shown that M-27, but not H-59 cells express high levels of the secretory leukocyte protease inhibitor SLPI, an 11.7-kd secreted molecule that can block nuclear factor-B-mediated TNF-␣ production in macrophages and thereby attenuate the host inflammatory response. 44 -46 We further demonstrated that SLPI production diminished the proinflammatory response triggered by the tumor cells and, as a consequence, reduced liver metastasis.…”

Section: Discussionmentioning

confidence: 99%

The Host Inflammatory Response Promotes Liver Metastasis by Increasing Tumor Cell Arrest and Extravasation

Auguste

Fallavollita

Wang

et al. 2007

The American Journal of Pathology

145

104

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Inflammation can play a regulatory role in cancer progression and metastasis. Previously, we have shown that metastatic tumor cells entering the liver trigger a proinflammatory response involving Kupffer cell-mediated release of tumor necrosis factor-␣ and the up-regulation of vascular endothelial cell adhesion receptors, such as E-selectin. Here, we analyzed spatio-temporal aspects of the ensuing tumor-endothelial cell interaction using human colorectal carcinoma CX-1 and murine carcinoma H-59 cells and a combination of immunohistochemistry, confocal microscopy, and threedimensional reconstruction. E-selectin expression was evident mainly on sinusoidal vessels by 6 and 10 hours, The host microenvironment plays an important role in the regulation of tumor progression at the primary site. It can also facilitate tumor dissemination by promoting neovascularization and providing growth-enhancing factors to the metastatic cells at the secondary sites of growth.

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Section: Discussionmentioning

confidence: 99%

The Host Inflammatory Response Promotes Liver Metastasis by Increasing Tumor Cell Arrest and Extravasation

Auguste

Fallavollita

Wang

et al. 2007

The American Journal of Pathology

145

104

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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%

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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“…8) that the hnRNP M4 is involved in a multiprotein complex that can recognize CEA on the surface of KC and initiate a series of signaling events that lead to the induction of IL-1␣, IL-6, IL-10, and tumor necrosis factor-␣ cytokines (10) and tyrosine phosphorylation (9). Based on this study three mechanisms of cytokine regulation by CEA can be envisioned.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that CEA is rapidly cleared from the circulation of experimental animals, accumulates in the liver, and is endocytosed in vitro by Kupffer cells. This initiates a series of signaling events that leads to tyrosine phosphorylation on at least two intracellular proteins (9) and is followed by induction of IL-1␣, IL-6, IL-10, and tumor necrosis factor-␣ cytokines (10). CEA uptake by Kupffer cells is independent of its carbohydrate composition and is mediated by an 80-kDa binding protein (11).…”

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confidence: 99%

Heterogeneous RNA-binding Protein M4 Is a Receptor for Carcinoembryonic Antigen in Kupffer Cells

Bajenova

Zimmer

Stolper

et al. 2001

Journal of Biological Chemistry

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Here we report the isolation of the recombinant cDNA clone from rat macrophages, Kupffer cells (KC) that encodes a protein interacting with carcinoembryonic antigen (CEA). To isolate and identify the CEA receptor gene we used two approaches: screening of a KC cDNA library with a specific antibody and the yeast two-hybrid system for protein interaction using as a bait the N-terminal part of the CEA encoding the binding site. The liver is a common site for metastasis from various forms of primary malignancies. Both experimental and clinical results reveal that the presence of carcinoembryonic antigen (CEA) 1 enhances liver metastasis from colorectal carcinoma cells (1, 2). CEA is a highly characterized, cell surface glycoprotein overexpressed by various tumor cells and provides a tool for tumor tissue-specific targeting. Increasing amounts of CEA in the serum correlates with the development of metastatic recurrence after surgical removal of the primary tumor (3). Earlier we have shown that CEA production of human colorectal cancer cell lines directly correlates with the metastatic potential (4). Poorly metastatic colon cancer cell lines become highly metastatic when transfected with the cDNA coding for CEA (5, 6). As a member of the immunoglobulin supergene family, CEA is involved in intercellular recognition and may facilitate attachment of colorectal carcinoma cells to sites of metastasis. In an experimental metastasis model of colorectal carcinoma in athymic nude mice, systemic injection of CEA enhanced experimental liver metastasis and implantation in liver by weakly metastatic tumor cells (7,8).To successfully treat cancers, it is necessary to prevent the development of metastasis after the treatment or removal of the primary malignancy. Therefore, it is important to elucidate the mechanism by which CEA enhances metastatic potential. The molecular basis by which CEA can influence metastasis is only partly understood. We have shown that CEA is rapidly cleared from the circulation of experimental animals, accumulates in the liver, and is endocytosed in vitro by Kupffer cells. This initiates a series of signaling events that leads to tyrosine phosphorylation on at least two intracellular proteins (9) and is followed by induction of IL-1␣, IL-6, IL-10, and tumor necrosis factor-␣ cytokines (10). CEA uptake by Kupffer cells is independent of its carbohydrate composition and is mediated by an 80-kDa binding protein (11). CEA is recognized by this binding protein through a 5-amino acid sequence, Pro-Glu-Leu-Pro-Lys (PELPK), located at the hinge region (amino acids 108 -112) between the N-terminal and the first immunoglobulin loop domain (12). Molecular modeling studies have suggested that this region is exposed on the surface of the molecule. 2 We have recently shown in a subset of colorectal cancer patients that mutations in the PELPK region of CEA results in the accumulation of large amounts of CEA in the serum (13). To further study the interaction between the peptide sequence, PELPK, and rat Kupffer cells, the...

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Carcinoembryonic antigen induces signal transduction in Kupffer cells

Cited by 23 publications

References 13 publications

The Host Inflammatory Response Promotes Liver Metastasis by Increasing Tumor Cell Arrest and Extravasation

The Host Inflammatory Response Promotes Liver Metastasis by Increasing Tumor Cell Arrest and Extravasation

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

Heterogeneous RNA-binding Protein M4 Is a Receptor for Carcinoembryonic Antigen in Kupffer Cells

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