Overexpression of CXCL1 and its receptor CXCR2 promote tumor invasion in gastric cancer

Ann Oncol. 2011 Oct;22(10):2267-76. doi: 10.1093/annonc/mdq739. Epub 2011 Feb 22.

Abstract

Background: The chemokine (C-X-C motif) ligand 1 (CXCL1) and its receptor CXCR2 are associated with metastasis potential. Our studies were designed to clarify the CXCL1 and CXCR2 expression patterns and to explore their potential role in gastric cancer.

Design: The expression of CXCL1 was determined in primary gastric cancer specimens using quantitative PCR, immunohistochemistry, and western blotting. To investigate the functional significance of CXCL1 expression, a CXCL1 expression vector and short hairpin RNA targeting the CXCL1 or CXCR2 were transfected into gastric cancer cell lines to examine the biological outcomes of these cells.

Results: The expression of CXCL1 and CXCR2 was higher in gastric cancer tissues compared with adjacent noncancerous tissues. The upregulation of CXCL1 correlated significantly with tumor progression, advanced stage of gastric cancer patients, and was one of the independent prognostic factors for patient's survival. Furthermore, cancer cells expressing CXCL1 stably exhibited an increase in their migration and invasion ability, whereas CXCL1 or CXCR2 depletion significantly reduced the migration and invasion ability of each cell line.

Conclusions: These results provide strong evidence that CXCL1 plays an important role in gastric cancer progression and migration and suggest that CXCL1 is a promising marker for the detection and prognosis of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Movement / physiology
  • Chemokine CXCL1 / biosynthesis*
  • Chemokine CXCL1 / blood
  • Chemokine CXCL1 / genetics
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis
  • Middle Aged
  • Neoplasm Invasiveness
  • Real-Time Polymerase Chain Reaction
  • Receptors, Interleukin-8B / biosynthesis*
  • Receptors, Interleukin-8B / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Up-Regulation

Substances

  • CXCL1 protein, human
  • CXCL8 protein, human
  • Chemokine CXCL1
  • Interleukin-8
  • Receptors, Interleukin-8B
  • MMP2 protein, human
  • Matrix Metalloproteinase 2