Gradient Infiltration of Neutrophil Extracellular Traps in Colon Cancer and Evidence for Their Involvement in Tumour Growth

PLoS One. 2016 May 2;11(5):e0154484. doi: 10.1371/journal.pone.0154484. eCollection 2016.


Background: The role of neutrophils in tumour biology is largely unresolved. Recently, independent studies indicated either neutrophil extracellular traps (NETs) or Tissue Factor (TF) involvement in cancer biology and associated thrombosis. However, their individual or combined role in colonic adenocarcinoma is still unexplored.

Methods: Colectomy tissue specimens and variable number of draining lymph nodes were obtained from ten patients with adenocarcinoma of the colon. NETs deposition and neutrophil presence as well as TF expression were examined by immunostaining. The effect of NETs on cancer cell growth was studied in in vitro co-cultures of Caco-2 cell line and acute myeloid leukemia primary cells. Proliferation and apoptosis/necrosis of cancer cells were analyzed by flow cytometry.

Results: TF-bearing NETs and neutrophil localization were prominent in tumour sections and the respective metastatic lymph nodes. Interestingly, neutrophil infiltration and NETs concentration were gradually reduced from the tumour mass to the distal margin. The in vitro-generated NETs impeded growth of cancer cell cultures by inducing apoptosis and/or inhibiting proliferation.

Conclusions: These data support further the role of neutrophils and NETs in cancer biology. We also suggest their involvement on cancer cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology*
  • Extracellular Traps / immunology
  • Extracellular Traps / physiology
  • Flow Cytometry
  • Humans
  • Neutrophil Infiltration / immunology*
  • Neutrophil Infiltration / physiology*
  • Neutrophils / immunology*
  • Neutrophils / physiology*
  • Tumor Cells, Cultured

Grant support

This project was supported by the Governing Board of the University Hospital of Alexandroupolis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.