title: Tissue-infiltrating plasma cells are an important source of carboxylesterase 2 contributing to the therapeutic efficacy of prodrugs.
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.
authors.affiliation: Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/ Research Center ImmunoSciences, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/ Research Center ImmunoSciences, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.affiliation: Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/ Research Center ImmunoSciences, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Cieluch
authors.affiliation: Medical Department, Division of Gastroenterology, Infectiology and Rheumatology/ Research Center ImmunoSciences, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Spieckermann
authors.affiliation: Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Gröne
authors.affiliation: Institute for Pathology, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lohneis
authors.affiliation: Medizinische Klinik, Hepatology & Gastroenterology, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Ulrich Frank
authors.initials: UF
authors.lastname: Pape
authors.affiliation: Institute for Pathology, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Ruza
authors.initials: R
authors.lastname: Arsenic
authors.affiliation: Institute for Medical Immunology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany. Electronic address: nalan.utku@charite.de.
authors.forename: Nalân
authors.initials: N
authors.lastname: Utku
mesh_terms: D065767:Activation, Metabolic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D043182:Carboxylesterase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004764:Enterohepatic Circulation; D005260:Female; D005765:Gastrointestinal Agents / Q000378:metabolism* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D019073:HT29 Cells; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019169:Jurkat Cells; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010950:Plasma Cells / Q000201:enzymology*; D011355:Prodrugs / Q000378:metabolism* / Q000627:therapeutic use; D020298:U937 Cells; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005765:Gastrointestinal Agents; D011355:Prodrugs; C517204:CES2 protein, human; D043182:Carboxylesterase
keywords: Colorectal cancer; Immunohistochemistry; Inflammatory bowel disease; Plasma cells; Tumors