TY - JOUR
T1 - Alcohol, carcinoembryonic antigen processing and colorectal liver metastases
AU - McVicker, Benita
AU - Tuma, Dean J.
AU - Lazure, Kathryn E.
AU - Thomas, Peter
AU - Casey, Carol A.
N1 - Publisher Copyright:
© Springer International Publishing Switzerland 2015
PY - 2014
Y1 - 2014
N2 - It is well established that alcohol consumption is related to the development of alcoholic liver disease. Additionally, it is appreciated that other major health issues are associated with alcohol abuse, including colorectal cancer (CRC) and its metastatic growth to the liver. Although a correlation exists between alcohol use and the development of diseases, the search continues for a better understanding of specifi c mechanisms. Concerning the role of alcohol in CRC liver metastases, recent research is aimed at characterizing the processing of carcino-embryonic antigen (CEA), a glycoprotein that is associated with and secreted by CRC cells. A positive correlation exists between serum CEA levels, liver metastasis, and alcohol consumption in CRC patients, although the mechanism is not understood. It is known that circulating CEA is processed primarily by the liver, fi rst by nonparenchymal Kupffer cells (KCs) and secondarily, by hepatocytes via the asialoglycoprotein receptor (ASGPR). Since both KCs and hepatocytes are known to be signifi cantly impacted by alcohol, it is hypothesized that alcohol-related effects to these liver cells will lead to altered CEA processing, including impaired asialo-CEA degradation, resulting in changes to the liver microenviron-ment and the metastatic potential of CRC cells. Also, it is predicted that CEA processing will affect cytokine production in the alcohol-injured liver, resulting in pro-metastatic changes such as enhanced adhesion molecule expression on the hepatic sinusoidal endothelium. This chapter examines the potential role that alcohol-induced liver cell impairments can have in the processing of CEA and associated mechanisms involved in CEA-related colorectal cancer liver metastasis.
AB - It is well established that alcohol consumption is related to the development of alcoholic liver disease. Additionally, it is appreciated that other major health issues are associated with alcohol abuse, including colorectal cancer (CRC) and its metastatic growth to the liver. Although a correlation exists between alcohol use and the development of diseases, the search continues for a better understanding of specifi c mechanisms. Concerning the role of alcohol in CRC liver metastases, recent research is aimed at characterizing the processing of carcino-embryonic antigen (CEA), a glycoprotein that is associated with and secreted by CRC cells. A positive correlation exists between serum CEA levels, liver metastasis, and alcohol consumption in CRC patients, although the mechanism is not understood. It is known that circulating CEA is processed primarily by the liver, fi rst by nonparenchymal Kupffer cells (KCs) and secondarily, by hepatocytes via the asialoglycoprotein receptor (ASGPR). Since both KCs and hepatocytes are known to be signifi cantly impacted by alcohol, it is hypothesized that alcohol-related effects to these liver cells will lead to altered CEA processing, including impaired asialo-CEA degradation, resulting in changes to the liver microenviron-ment and the metastatic potential of CRC cells. Also, it is predicted that CEA processing will affect cytokine production in the alcohol-injured liver, resulting in pro-metastatic changes such as enhanced adhesion molecule expression on the hepatic sinusoidal endothelium. This chapter examines the potential role that alcohol-induced liver cell impairments can have in the processing of CEA and associated mechanisms involved in CEA-related colorectal cancer liver metastasis.
KW - Alcoholic liver disease
KW - Asialoglycoprotein receptor
KW - Carcinoembryonic antigen
KW - Carcinoembryonic antigen receptor
KW - Colorectal cancer
KW - Kupffer cells
KW - Liver metastases
KW - Liver microenvironment
KW - Pro-inflammatory cytokines
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U2 - 10.1007/978-3-319-09614-8_17
DO - 10.1007/978-3-319-09614-8_17
M3 - Article
C2 - 25427914
AN - SCOPUS:84925324978
SN - 0065-2598
VL - 815
SP - 295
EP - 311
JO - Advances in experimental medicine and biology
JF - Advances in experimental medicine and biology
ER -