Journal
CELLULAR IMMUNOLOGY
Volume 283, Issue 1-2, Pages 61-69Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2013.06.005
Keywords
Myeloid-derived suppressor cells; Neo-angiogenesis; SSAO inhibitors; Tumor growth; Vascular adhesion protein-1
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Funding
- National Natural Science Foundation of China [81170315]
- Ministry of Science and Technology [2010CB912503]
- Guangdong Natural Science Foundation [9351503102000001]
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Vascular adhesion protein-1 (VAP-1) is both an endothelial adhesion molecule involved in leukocytes emigration, and an oxidase belonging to the family of semicarbazide-sensitive amine oxidases (SSAOs). The enzyme activity of VAP-1 plays an important role in the migration of myeloid-derived suppressor cells (MDSCs) into tumor site, and SSAO inhibitors can block the function of VAP-1. The effects of SSAO inhibitors on leukocyte infiltration and tumor progression were evaluated in H22 hepatocellular carcinoma-bearing C57BL/6 mice. Tumor weight and volume were measured after SSAO inhibitor treatment. Then, MDSCs recruitment and neo-angiogenesis were determined using immunostaining. SSAO inhibitors significantly blocked the catalytic activity of VAP-1 in tumor, attenuated tumor progression, and reduced neo-angiogenesis. CD11b(+) and Gr-1(+) MDSCs, which normally infiltrate into tumors, were significantly diminished in tumor-bearing mice treated with SSAO inhibitors. The present study demonstrated that SSAO inhibitors might have an anti-tumor effect on hepatocellular carcinoma by inhibiting recruitment of CD11b(+) and Gr-1(+) cells and hindering angiogenesis, which could be attributed to impairing the catalytic activity of VAP-1. (C) 2013 Elsevier Inc. All rights reserved.
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