Role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinomas

Hum Pathol. 2012 Dec;43(12):2299-307. doi: 10.1016/j.humpath.2011.08.027. Epub 2012 Aug 3.

Abstract

The chemokine ligand CXC chemokine ligand 16 and its receptor chemokine (C-X-C motif) receptor 6 are up-regulated in many types of cancer and give rise to more aggressive behavior by regulating proliferation and angiogenesis. To clarify the role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinoma, their expression was examined by immunohistochemistry of tissue microarrays containing gastric carcinoma and nonneoplastic mucosa, reverse transcription-polymerase chain reaction, and Western blotting and by enzyme-linked immunosorbent assay to determine the CXC chemokine ligand 16 concentration in serum. Expression was compared with the clinicopathologic features of the carcinomas. All carcinoma and epithelial cells showed CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 messenger RNA expression to various degrees. Among 28 pairs of gastric carcinoma and normal tissues, there was higher CXC chemokine ligand 16 expression in carcinoma than in adjacent mucosa (P < .05), whereas the converse was true for chemokine (C-X-C motif) receptor 6 (P < .05). Nuclear CXC chemokine ligand 16 expression correlated inversely with the depth of invasion, lymphatic invasion, Union Internationale Contre le Cancer stage, and favorable prognosis. The serum CXC chemokine ligand 16 concentration was lower in male patients or patients 55 years or older than in female or younger patients, respectively (P < .05). Patients with lymphatic invasion or mixed-type carcinoma showed lower CXC chemokine ligand 16 concentrations than those with no lymphatic invasion or with diffuse-type carcinoma (P < .05). Aberrant expression of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 might be involved in gastric carcinogenesis. The expression and serum concentration of CXC chemokine ligand 16 could indicate the aggressiveness and prognosis of gastric carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Chemokine CXCL16
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Disease Progression
  • Female
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, CXCR6
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / metabolism*
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Sex Factors
  • Stomach / pathology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • CXCL16 protein, human
  • CXCR6 protein, human
  • Chemokine CXCL16
  • Chemokines, CXC
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Scavenger
  • Receptors, Virus