INSL5 is a novel marker for human enteroendocrine cells of the large intestine and neuroendocrine tumours

Oncol Rep. 2013 Jan;29(1):149-54. doi: 10.3892/or.2012.2119. Epub 2012 Oct 31.


We report for the first time the distribution of human INSL5 and its cognate leucine rich G-protein coupled receptor RXFP4 in the large intestine and in neuroendocrine/carcinoid tissues. Immunoreactive INSL5 was uniquely expressed by enteroendocrine cells (EECs) located within the colonic mucosa, whereas colonocytes were immunopositive for RXFP4. INSL5+ and RXFP4+ cells were also detected in human neuroendocrine/carcinoid tissues. We employed a recently described Insl5 knockout mouse model and 2 mouse models of induced colitis to address the relevance of Insl5 in EEC development and in acute inflammation of the colon. We identified INSL5 as a specific marker for synaptophysin+ EECs in the mucosa of the normal human and mouse colon. Insl5 was not essential for the development of mouse synaptophysin+ EECs. The mouse models of chemically induced colitis (dextran sulfate sodium and dinitrobenzene-sulfonic acid) failed to show changes in the numbers of Insl5+ EECs at inflammatory sites during the acute phase of colitis. In conclusion, we showed that INSL5 is a novel marker of colorectal EECs and provide first evidence for the presence of a potentially autocrine/paracrine INSL5-RXFP4 signaling system in the normal human and mouse colon and in rare human neuroendocrine tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication
  • Biomarkers, Tumor / analysis*
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology*
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Enteroendocrine Cells / metabolism
  • Enteroendocrine Cells / pathology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin / physiology*
  • Intestine, Large / metabolism
  • Intestine, Large / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • Neoplasm Staging
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology*
  • Paracrine Communication
  • Prognosis
  • Proteins / physiology*
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Peptide / metabolism*
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • Insulin
  • Leydig insulin-like protein
  • Proteins
  • RXFP4 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Dextran Sulfate