Comprehensive evaluation of carboxylesterase-2 expression in normal human tissues using tissue array analysis.
Carboxylesterases play an important role in the hydrolytic biotransformation of a number of structurally diverse endogenous compounds and medications. Several distinct carboxylesterase isoforms have been described in human liver, brain, and placenta. Carboxylesterase-2 has been identified as the key enzyme in the metabolic activation of the irinotecan, a topoisomerase I inhibitor commonly used in the treatment of many solid tumors. The tissue distribution and intensity of protein expression of carboxylesterase-2 have not been defined in any organ or tissue. This study used a carboxylesterase-2-specific antibody and tissue array analysis to detect carboxylesterase-2 expression in human normal tissues by immunohistochemistry. Carboxylesterase-2 is present in a wide variety of organs and tissues. The highest carboxylesterase-2 expression occurs in hepatocyte, small intestine mucosa, kidney proximal convoluted tubule, and adrenal cortex cells. The results suggest that liver and gastrointestinal tract with carboxylesterase-2 are likely the most important sites of conversion of irinotecan to the active metabolite SN-38, but carboxylesterase-2 within the other tissues may be contributive to this process. In the central nervous system, carboxylesterase-2 expression was confined to capillary endothelial cells, consistent with the enzyme having a role to protect the central nervous system from toxic esters and perhaps being a component of a blood-brain barrier system.
Zhang
Wanghai
W
Washington University School of Medicine, Department of Medicine, Siteman Cancer Center, St. Louis, Missouri 63110, USA.
Xu
Guang
G
McLeod
Howard L
HL
D000595:Amino Acid Sequence; D000906:Antibodies; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007527:Isoenzymes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution
D000906:Antibodies; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases