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SDF-1α upregulation of MMP-2 is mediated by p38 MAPK signaling in pancreatic cancer cell lines

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Abstract

Pancreatic cancer is highly invasive and is currently the fourth leading cause of cancer death worldwide. CXC chemokine receptor-4 (CXCR4) is a G protein-coupled receptor for CXC chemokine ligand 12/stromal cell-derived factor-1α (SDF-1α), a member of a large family of small, structurally related, heparin-binding chemokine proteins. SDF-1α/CXCR4 plays an important role in tumor growth, invasion, metastasis, and angiogenesis. SDF-1α and CXCR4 are upregulated in many tumors, including pancreatic cancer tissues, and preliminary data indicate that the SDF-1/CXCR4 axis plays an important role in tumor invasion. However, their precise role and the mechanism through which they function remain largely unknown. In this study, analysis of SDF-1α, CXCR4 and MMP-2 expression in pancreatic cancer and adjacent tissue samples from ten patients revealed that all three proteins are overexpressed in human pancreatic cancer. SDF-1α induced MMP-2 and MMP-9 upregulation in PANC-1 and SW-1990 cells, which was associated with increased pancreatic cancer cell proliferation and invasion. Furthermore, SDF-1α induced p38 phosphorylation and p38 inhibition reduced both the level of SDF-1α-stimulated MMP-2 expression and PANC-1 cell invasion. Overall, our results demonstrate that SDF-1α/CXCR4 upregulates MMP-2 expression and induces pancreatic cancer cell invasion in PANC-1 and SW-1990 cell lines by activating p38 MAPK.

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Acknowledgments

This work was supported by grants from Science and Technology Support Program of Huaian (No. HAS2010023).

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Authors and Affiliations

  1. Department of Gastroenterology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300, Jiangsu, People’s Republic of China

    Feng Pan, Shijie Ma, Weike Cao, Haining Liu & Fengli Chen

  2. Department of Oncology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300, Jiangsu, People’s Republic of China

    Xiaofei Chen

  3. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Ruihua Shi

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  1. Feng Pan
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  2. Shijie Ma
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  3. Weike Cao
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  4. Haining Liu
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  5. Fengli Chen
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  6. Xiaofei Chen
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Correspondence to Xiaofei Chen or Ruihua Shi.

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Feng Pan and Shijie Ma contributed equally to this study.

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Pan, F., Ma, S., Cao, W. et al. SDF-1α upregulation of MMP-2 is mediated by p38 MAPK signaling in pancreatic cancer cell lines. Mol Biol Rep 40, 4139–4146 (2013). https://doi.org/10.1007/s11033-012-2225-4

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  • DOI: https://doi.org/10.1007/s11033-012-2225-4

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