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Cancer Lett. 2016 Aug 1;378(1):51-8. doi: 10.1016/j.canlet.2016.04.041. Epub 2016 May 2.

Tissue-infiltrating plasma cells are an important source of carboxylesterase 2 contributing to the therapeutic efficacy of prodrugs.

Author information

1
Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/ Research Center ImmunoSciences, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
2
Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
3
Institute for Pathology, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany.
4
Medizinische Klinik, Hepatology & Gastroenterology, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany.
5
Institute for Medical Immunology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany. Electronic address: nalan.utku@charite.de.

Abstract

Carboxylesterase 2 (CES-2) is instrumental for conversion of ester-containing prodrugs in cancer treatment. CES-2 expression was analyzed by immunohistochemistry in colorectal cancer (CRC) compared to colonic inflammation as well as in liver and peripheral blood. In CRC, tumor grades showed no correlation with levels of CES-2 expression, which was heterogeneous within these tumors. Cellular infiltrates in the immediate tumor vicinity expressed high levels of CES-2. Thus, tissue adjacent to the tumor was a substantial source of CES-2 with high expression in plasma cells. CES-2(high) plasma cells were abundantly found in the colon of patients with inflammatory bowel disease. CES-2 expression is strong in hepatocytes of normal livers, while CES-2 expression in peripheral blood mononuclear cells of healthy donors was overall low at protein and mRNA levels. In summary, the conversion of ester-containing prodrugs by CES-2 is mainly to occur in the periphery, during liver passage and in the colon after enterohepatic recirculation. We here demonstrated plasma cells as strong producers of CES-2. Further studies should elucidate the role of CES-2(+) plasma cells in intestinal inflammation and cancer.

KEYWORDS:

Colorectal cancer; Immunohistochemistry; Inflammatory bowel disease; Plasma cells; Tumors

PMID:
27149931
DOI:
10.1016/j.canlet.2016.04.041
[Indexed for MEDLINE]

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