title: SSAO inhibitors suppress hepatocellular tumor growth in mice.
abstract: 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.
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Luo
authors.forename: Zhe-Xuan
authors.initials: ZX
authors.lastname: Lin
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Jiang
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Luo
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006631:Amine Oxidase (Copper-Containing)
keywords: HYD; LJP1207; MAO-A; MAO-B; MDSCs; Myeloid-derived suppressor cells; Neo-angiogenesis; N′-[2-phenyl-allyl]-hydrazine hydrochloride; PBS; SEM; SSAO; SSAO inhibitors; Tumor growth; VAP-1; Vascular adhesion protein-1; hydralazine; monoamine oxidase-A; monoamine oxidase-B; myeloid-derived suppressor cells; phosphate buffer saline; semicarbazide; semicarbazide-sensitive amine oxidase; vascular adhesion protein-1