title: Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma.
abstract: Lymph node metastasis is a major prognostic factor for patients with breast cancer. The activation of vascular endothelial growth factor (VEGF)-C plays a key role in lymph node metastasis through promoting lymphangiogenesis. Thus, we attempted to elucidate whether small interfering RNAs (siRNA) targeting VEGF-C could suppress lymphangiogenesis and lymph node metastasis in vivo. A lentivirus-based VEGF-C siRNA vector was infected into breast cancer cells and a xenograft model. The expression of VEGF-C mRNA and protein were quantified by quantitative real-time polymerase chain reaction (QRT-PCR), immunohistochemistry, and western blot analysis. The effect of VEGF-C siRNA on breast cancer cells was investigated by an invasion assay. Lymphangiogenesis was analyzed with anti-LYVE-1 and anti-D2-40 by immunohistochemical analysis. Lentivirus-mediated VEGF-C siRNA stably reduced VEGF-C mRNA and protein expression. VEGF-C siRNA inhibited the invasive ability of breast cancer cells in vitro. Five weeks after intratumoral injection, the tumor volume was significantly smaller in the VEGF-C siRNA group than in the control scramble siRNA group in the MDA-MB-231 cell xenograft model. The numbers of LYVE-1 and D2-40 positive vessels per microscopic field were significantly decreased in the VEGF-C siRNA group, which indicates that VEGF-C siRNA inhibited lymphangiogenesis. Moreover, lymph node metastasis was significantly suppressed by VEGF-C siRNA in vivo. In conclusion, these results indicate that lentivirus-mediated VEGF-C siRNA offers a new approach for therapeutic intervention to prevent tumor growth and lymphatic metastasis of breast cancer.
authors.affiliation: Department of General Surgery, The Second Clinical Hospital, Harbin Medical University, Harbin, China.
authors.forename: Baoliang
authors.initials: B
authors.lastname: Guo
authors.forename: Yafang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guoqing
authors.initials: G
authors.lastname: Luo
authors.forename: Lichun
authors.initials: L
authors.lastname: Li
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D016896:Treatment Outcome; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse