Pancreatic stellate cells increase the invasion of human pancreatic cancer cells through the stromal cell-derived factor-1/CXCR4 axis

Pancreatology. 2010;10(2-3):186-93. doi: 10.1159/000236012. Epub 2010 May 17.

Abstract

Aim: Both pancreatic stellate cells (PSCs) and the stromal cell-derived factor-1(SDF-1)/CXCR4 receptor ligand system have important roles in pancreatic cancer progression. This study set out to detect if PSCs express SDF-1 and promote the invasion of pancreatic cancer through the SDF-1/CXCR4 receptor ligand axis.

Methods: RT-PCR was performed to detect the expression of SDF-1 and CXCR4 in PSCs, pancreatic cancer lines and cancer tissue samples. ELISA was used to investigate the concentration of SDF-1 in PSC supernatants. An MTT assay was applied to detect the proliferation of pancreatic cancer cells. A transwell chamber migration assay was employed to detect the migration of AsPC-1 cells. An in vitro invasion assay was used to detect the invasion of AsPC-1 cells.

Results: CXCR4 expression was detected in PSCs; AsPC-1, SW1990 and BxPC-3 cancer cells; and cancer tissues. SDF-1 was detected in PSCs and cancer tissues, but not in AsPC-1, SW1990 and BxPC-3 cells. SDF-1alpha protein was found in PSC supernatants. PSC-conditioned media can promote the proliferation, migration and invasion of pancreatic cancer cells. SDF-1 neutralizing antibody or AMD3100 can significantly inhibit these promotive and IAP.

MeSH terms

  • Cell Line, Tumor
  • Chemokine CXCL12 / physiology*
  • Culture Media, Conditioned / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness / physiopathology*
  • Pancreas / cytology*
  • Pancreatic Neoplasms / physiopathology*
  • Receptors, CXCR4 / physiology*

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Culture Media, Conditioned
  • Receptors, CXCR4