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CXCL12-CXCR4 Promotes Proliferation and Invasion of Pancreatic Cancer Cells

  • Shen, Bo (Department of Medical Oncology, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Zheng, Ma-Qing (School of Pharmacy, Nanjing University of Technology) ;
  • Lu, Jian-Wei (Department of Medical Oncology, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Jiang, Qian (Department of Surgical Oncology, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Wang, Tai-Hong (Department of Surgical Oncology, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Huang, Xin-En (Department of Medical Oncology, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research)
  • Published : 2013.09.30

Abstract

Objective: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. Methods: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. Results: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP-9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). Conclusions: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.

Keywords

CXCL12;CXCR4;AMD3100;pancreatic cancer;proliferation;invasion

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