Mast cells co-expressing CD68 and inorganic polyphosphate are linked with colorectal cancer

PLoS One. 2018 Mar 15;13(3):e0193089. doi: 10.1371/journal.pone.0193089. eCollection 2018.

Abstract

Inflammation is a hallmark of colorectal cancer (CRC). Neutrophils are well-known mediators in tumor biology but their role in solid tumors, including CRC, was redefined by neutrophil extracellular traps (NETs). Given that it was recently demonstrated that platelet-derived polyP primes neutrophils to release NETs, we examined surgical specimens from CRC to investigate the presence of polyP, as a possible NET inducer. Biopsies with adenomas, hyperplastic polyps, inflammatory bowel disease and healthy colon tissues were used as controls. In all cases, the presence of polyP was apparent, with the main source of polyP being the mast cells. In all CRC and all adenomas with high-grade dysplasia, a substantial number of mast cells, more than 50%, co-expressed intracellularly polyP with CD68 surface antigen (CD68+), but this was not the case in the other examined disorders. PolyP-expressing mast cells were detected in close proximity with tumor cells and neutrophils, suggesting polyP expression by CD68+ mast cells among the stimuli which prime neutrophils to release NETs, in CRC. Moreover, the detection of CD68+ polyP-expressing mast cells could represent a potential prognostic marker in colorectal adenomas and/or carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma* / metabolism
  • Adenoma* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / biosynthesis*
  • Antigens, Differentiation, Myelomonocytic / biosynthesis*
  • Antigens, Neoplasm / biosynthesis*
  • Biomarkers, Tumor / biosynthesis*
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mast Cells* / metabolism
  • Mast Cells* / pathology
  • Middle Aged
  • Polyphosphates / metabolism*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CD68 antigen, human
  • Polyphosphates

Grant support

This study was supported by the Scientific Committee of Democritus University of Thrace Grant number - 80895. Mr. Athanasios Arampatzioglou was also supported by the European Union (European Social Fund - ESF) and Greek national funds through the action entitled ”Strengthening Human Resources Research Potential via Doctorate Research” of State Scholarships Foundation (IKY), in the framework of the Operational Programme ”Human Resources Development Program, Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) 2014–2020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.