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: Baoliang Guo, Yafang Zhang, Guoqing Luo, Lichun Li, Jianguo Zhang
• Journal: Anatomical record (Hoboken, N.J. : 2007) (Anat Rec (Hoboken)) Vol. 292 Issue 5 Pg. 633-9 (May 2009) ISSN: 1932-8494 [Electronic] United States
• PMID: 19382240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Vascular Endothelial Growth Factor C
• vascular endothelial growth factor C, mouse

Topics

• Animals
• Breast Neoplasms (genetics, metabolism, therapy)
• Carcinoma (genetics, metabolism, therapy)
• Cell Line, Tumor
• Disease Models, Animal
• Down-Regulation (genetics)
• Female
• Gene Targeting (methods)
• Genetic Therapy (methods)
• Genetic Vectors (genetics)
• Humans
• Lentivirus (genetics)
• Lymphatic Vessels (metabolism, pathology, physiopathology)
• Mice
• Mice, Nude
• Neoplasm Invasiveness (genetics, prevention & control)
• Neovascularization, Pathologic (genetics, metabolism, therapy)
• RNA Interference (physiology)
• RNA, Small Interfering (genetics, pharmacology)
• Treatment Outcome
• Vascular Endothelial Growth Factor C (antagonists & inhibitors, genetics, metabolism)