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Apoptosis and anergy of T cell induced by pancreatic stellate cells-derived galectin-1 in pancreatic cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Galectin-1, a β-galactoside-binding protein implicated in cancer cell immune privilege, was highly expressed in activated pancreatic stellate cells (PSCs). This study was designed to investigate the relationship between PSC-derived galectin-1 and tumor immunity in pancreatic cancer. Isolated PSCs were identified as normal pancreas cells (hNPSCs) or pancreatic cancer cells (hCaPSCs) by immunohistochemical staining for α-SMA and vimentin, and galectin-1 expression was evaluated by Western blotting and quantitative RT-PCR. Apoptosis, caspase activity, and cytokine production (IL-6, IL-10, TNF-β, and IFN-γ) of T cells co-cultured with PSCs were evaluated, and immunohistochemical staining of galectin-1 was correlated with CD3 and clinicopathological variables in 66 pancreatic cancer and 10 normal pancreatic tissue samples. hCaPSCs exhibited higher galectin-1 expression than did hNPSCs, and hCaPSCs induced higher levels of apoptosis in T cells following co-culture. hCaPSCs activated caspase-9 and caspase-3 in the mitochondrial apoptotic pathway and stimulated secretion of Th2 cytokines (IL-6 and IL-10) but decreased secretion of Th1 cytokines (TNF-β and IFN-γ), compared with hNPSCs. Immunohistochemical staining indicated that galectin-1 and CD3 were more highly expressed in pancreatic cancer tissue. Galectin-1 expression was highest in poorly differentiated pancreatic cancer cells and lowest in well-differentiated pancreatic cancer cells and was associated with tumor size, lymph node metastasis, differentiation, and UICC stage. However, CD3 expression showed the opposite trend and was highest in well-differentiated pancreatic cancer cells and was associated with tumor differentiation and UICC stage. High expression of galectin-1 was associated with short survival, as was low expression of CD3. hCaPSC-derived galectin-1 enhanced apoptosis and anergy of T cells in pancreatic cancer, which contributes to the immune escape of pancreatic cancer cells.

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Acknowledgments

The authors wish to thank the staff of the Virology Laboratory at the Medical College of YangZhou University for their assistance. This work was supported by grants from the Postdoctoral Science Foundation of China (No. 2013M530243), the Social Development of Science and Technology Research Projects of Yangzhou City (No. 2012123), the Jiangsu Province Natural Science Foundation of China (BK20140495), and the Six Big Talent Peak Projects of Jiangsu Province (2014-WSW-078).

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    Authors and Affiliations

    1. Department of General Surgery, Clinical Medical College, Yangzhou University (Subei People’s Hospital of Jiangsu Province), Yangzhou, 225001, China

      Dong Tang, Jun Gao, Nianyuan Ye, Yang Chong, Chuanqi Xu, Xuetong Jiang, Bin Li, Wei Yin & Daorong Wang

    2. College of Clinical Medicine, Nanjing Medical University (The First Affiliated Hospital of Nanjing Medical University), Nanjing, 211166, China

      Sen Wang

    3. Department of General Surgery, Anhui No. 2 Provincial People’s Hospital, Hefei, 230012, China

      Zhongxu Yuan

    4. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

      Yi Miao & Kuirong Jiang

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    Correspondence to Daorong Wang or Kuirong Jiang.

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    Dong Tang and Jun Gao contributed equally to this work.

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    Tang, D., Gao, J., Wang, S. et al. Apoptosis and anergy of T cell induced by pancreatic stellate cells-derived galectin-1 in pancreatic cancer. Tumor Biol. 36, 5617–5626 (2015). https://doi.org/10.1007/s13277-015-3233-5

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