The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
Cell Immunol. 2013 May-Jun;283(1-2):61-9. doi: 10.1016/j.cellimm.2013.06.005. Epub 2013 Jun 24.
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.
血管黏附蛋白-1（VAP-1）既是一种参与白细胞迁移的内皮黏附分子，也是一种属于氨基脲敏感胺氧化酶（SSAO）家族的氧化酶。VAP-1 的酶活性在髓系来源抑制细胞（MDSCs）向肿瘤部位迁移中发挥重要作用，SSAO 抑制剂可以阻断 VAP-1 的功能。本研究在 H22 肝癌荷瘤 C57BL/6 小鼠中评估了 SSAO 抑制剂对白细胞浸润和肿瘤进展的影响。在 SSAO 抑制剂处理后测量肿瘤重量和体积。然后，使用免疫染色法测定 MDSCs 募集和新生血管形成。SSAO 抑制剂显著抑制了肿瘤中 VAP-1 的催化活性，减弱了肿瘤进展，并减少了新生血管形成。在接受 SSAO 抑制剂治疗的荷瘤小鼠中，正常浸润肿瘤的 CD11b(+)和 Gr-1(+) MDSCs 明显减少。本研究表明，SSAO 抑制剂可能通过抑制 CD11b(+)和 Gr-1(+)细胞的募集和抑制血管生成来发挥对肝癌的抗肿瘤作用，这可能归因于削弱了 VAP-1 的催化活性。
