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Related Experiment Videos

Comprehensive evaluation of carboxylesterase-2 expression in normal human tissues using tissue array analysis.

Wanghai Zhang1, Guang Xu, Howard L McLeod

  • 1Washington University School of Medicine, Department of Medicine, Siteman Cancer Center, St. Louis, Missouri 63110, USA.

Applied Immunohistochemistry & Molecular Morphology : AIMM
|February 28, 2003
PubMed
Summary

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Carboxylesterase-2 (CES2) is widely expressed in human tissues, with highest levels in the liver and small intestine. This enzyme is crucial for activating irinotecan, a chemotherapy drug, into its active form.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Human Anatomy

Background:

  • Carboxylesterases (CES) are enzymes involved in metabolizing various compounds.
  • Carboxylesterase-2 (CES2) is the primary enzyme responsible for activating irinotecan, a key chemotherapy agent.
  • The tissue distribution of CES2 has not been previously characterized.

Purpose of the Study:

  • To determine the tissue distribution and expression levels of Carboxylesterase-2 (CES2) in normal human tissues.
  • To identify potential sites for irinotecan metabolic activation.

Main Methods:

  • Immunohistochemistry using a CES2-specific antibody.
  • Tissue array analysis of normal human tissues.

Main Results:

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  • CES2 is expressed in a broad range of human organs and tissues.
  • Highest CES2 expression was observed in hepatocytes, small intestine mucosa, kidney proximal convoluted tubules, and adrenal cortex cells.
  • CES2 expression in the brain was limited to capillary endothelial cells.

Conclusions:

  • The liver and gastrointestinal tract are likely major sites for irinotecan activation to SN-38 due to high CES2 expression.
  • CES2 in other tissues may also contribute to irinotecan metabolism.
  • CES2 in brain capillary endothelial cells suggests a role in protecting the central nervous system.