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

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

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.

MeSH terms

  • Activation, Metabolic
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Carboxylesterase / blood
  • Carboxylesterase / genetics
  • Carboxylesterase / metabolism*
  • Colon / enzymology
  • Colon / pathology
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Enterohepatic Circulation
  • Female
  • Gastrointestinal Agents / metabolism*
  • Gastrointestinal Agents / pharmacology
  • Gene Expression Regulation, Enzymologic
  • HEK293 Cells
  • HT29 Cells
  • Hepatocytes / enzymology
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / enzymology*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / pathology
  • Jurkat Cells
  • K562 Cells
  • Leukocytes, Mononuclear / enzymology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Plasma Cells / enzymology*
  • Prodrugs / metabolism*
  • Prodrugs / therapeutic use
  • U937 Cells
  • Young Adult

Substances

  • Antineoplastic Agents
  • Gastrointestinal Agents
  • Prodrugs
  • CES2 protein, human
  • Carboxylesterase