Carcinoembryonic antigen promotes tumor cell survival in liver through an IL-10-dependent pathway

Wang

et al. 2010

Cell Biochem Biophys

Small-cell lung cancer (SCLC) is classified into two stages, limited-stage small-cell lung cancer (LS-SCLC) and extensive-stage small-cell lung cancer (ES-SCLC), with ES-SCLC being associated with reduced survival. However, disease stage alone is not a very precise predictor of survival time. The aim of this study is to search for a prognostic indicator that can be used in conjunction with the staging system in SCLC. We performed a prospective analysis of 116 patients with SCLC undergoing standard chemotherapy with or without radiotherapy. Expression levels of 12 tumor markers were measured at the time of diagnosis by a commercial protein chip system, and patients were followed up for a maximum of 54 weeks. CEA was the most frequently detected tumor marker in SCLC, with 32.8% of samples scoring positive, and was also the only marker that correlated with overall survival. The average survival time was 16.78 months for patients with CEA below 5 ng/ml and 11.4 months for patients with CEA above 5 ng/ml (P < 0.001). In contrast, no association was found between tumor stage and overall survival. CEA expression was independent of tumor stage (P = 0.930). CEA is an independent prognostic factor that can be used in conjunction with disease stage in SCLC.

Section: Discussionmentioning

confidence: 99%

CEA is an Independent Prognostic Indicator that is Associated with Reduced Survival and Liver Metastases in SCLC

Wang

et al. 2010

Cell Biochem Biophys

“…The last observation was further investigated and it was revealed that CEA supports CRC cell survival via the induction of IL-10 and subsequent decrease of NO concentration. IL-10 is probably released by stimulated KCs and NO levels decrease due to inhibition of inducible nitric oxide synthetase [146] . Accumulating data have demonstrated the important role of immunoglobulin superfamily adhesion molecules in colorectal liver metastases, referring to KCs.…”

Section: Kupffer Cellsmentioning

confidence: 99%

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

Paschos

Majeed

Bird

2014

WJG

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.

“…Tumor cells arresting in the liver also produce toxic levels of NO and reactive oxygen species (ROS) due to the creation of local ischemic/reperfusion injury [114]. The release of the antiinflammatory cytokine IL-10 by Kupffer cells activated by CEA also plays a role in tumor cell survival by inhibiting inducible nitric oxide synthetase (iNOS) and the production of NO and ROS, thus aiding tumor cell survival [115,116]. Hypoxia also up-regulates CEA expression in colorectal and breast cancers [117] this could be a defensive mechanism as release of CEA would activate Kupffer cells to produce more IL-10 and protect the cancer cells from the cytotoxic effects of NO and ROS.…”

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

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.