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Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression

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Tumor Biology

Abstract

Background

Galectin-1, an evolutionarily conserved glycan-binding protein with angiogenic potential, was recently identified as being overexpressed in cancer-associated fibroblasts (CAFs) of gastric cancer. The role of endogenous CAF-derived galectin-1 on angiogenesis in gastric cancer and the mechanism involved remain unknown.

Methods

Immunohistochemical staining was used to investigate the correlation between galectin-1 and vascular endothelial growth factor (VEGF) and CD31 expression in gastric cancer tissues and normal gastric tissues. Galectin-1 was knocked down in CAFs isolated from gastric cancer using small interfering ribonucleic acid (RNA), or overexpressed using recombinant lentiviruses, and the CAFs were co-cultured with human umbilical vein endothelial cells (HUVECs) or cancer cells. Subsequently, proliferation, migration, tube formation, and VEGF/VEGF receptor (VEGFR) 2 expression were detected. The role of CAF-derived galectin-1 in tumor angiogenesis in vivo was studied using the chick chorioallantoic membrane (CAM) assay.

Results

Galectin-1 was highly expressed in the CAFs and was positively associated with VEGF and CD31 expression. In the co-culture, high expression of galectin-1 in the CAFs increased HUVEC proliferation, migration, tube formation, and VEGFR2 phosphorylation and enhanced VEGF expression in gastric cancer cells. The CAM assay indicated that high expression of galectin-1 in the CAFs accelerated tumor growth and promoted angiogenesis. In contrast, galectin-1 knockdown in the CAFs significantly inhibited this effect.

Conclusion

CAF-derived galectin-1 significantly promotes angiogenesis in gastric cancer and may be a target for angiostatic therapy.

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Acknowledgments

We thank Prof. Lu Chun (Department of Microbiology and Immunology, Nanjing Medical University, China) for kindly providing the lentiviral packaging system consisting of pHAGE-CMV-MCS-IZs Green, psPAX2, and pMD2.G. We would like to thank the native English speaking scientists of Elixigen Company for editing our manuscript.

Conflicts of interest

None

Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81172279).

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    Authors and Affiliations

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

      Dong Tang, Jun Gao, Nianyuan Ye, Yang Chong, Yuqin Huang, Jie Wang, Bin Li, Wei Yin & Daorong Wang

    2. College of Clinical Medicine, Nanjing Medical University (the First Affiliated Hospital of Nanjing Medical University), Nanjing, 211166, People’s Republic of China

      Sen Wang

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    1. Dong Tang
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    Correspondence to Daorong Wang.

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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. Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression. Tumor Biol. 37, 1889–1899 (2016). https://doi.org/10.1007/s13277-015-3942-9

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    • DOI: https://doi.org/10.1007/s13277-015-3942-9

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