Therapy with siRNA for Vegf-c but not for Vegf-d suppresses wide-spectrum organ metastasis in an immunocompetent xenograft model of metastatic mammary cancer.
Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. Vascular endothelial growth factors-C and D (VEGF-C and VEGF-D) are heavily involved in lymphangiogenesis. Using small interfering RNA (siRNA) against mouse Vegf-c, and Vegf-d, we sought to inhibit metastasis in a model of metastatic murine mammary cancer. BJMC3879Luc2 cell-induced mammary carcinomas received direct intratumoral injections in vivo of either plasmid VEGF-C/D siRNA (psiVEGF-C, psiVEGF-D) or a vector control followed by in vivo gene electrotransfer weekly for seven weeks. Treatment with psiVEGF-C and with psiVEGF-D resulted in lower tumor volumes as compared to the controls. Treatment with psiVEGF-C suppressed wide-spectrum organ metastasis involving lung and lymph nodes. Treatment with psiVEGF-C further reduced the number of dilated lymphatic vessels with invading cancer cells and inhibited tumor blood microvessel density. In contrast, although treatment with psiVEGF-D was not effective and gave equivocal results, it did induce some insignificant reduction in tumor volume increment, average numbers of lymph node metastases and average number of intratumoral dilated lymphatic vessels. In conclusion, specific silencing of the Vegf-c gene suppresses wide-spectrum organ metastasis, including the lung and lymph nodes. However, therapy with siRNA for Vegf-d was not adequately effective in this murine system.
['Shibata|Masa-Aki|MA|', 'Shibata|Eiko|E|', 'Morimoto|Junji|J|', 'Harada-Shiba|Mariko|M|']
D000230:Adenocarcinoma D000818:Animals D004195:Disease Models, Animal D005260:Female D015316:Genetic Therapy D007121:Immunocompetence D008175:Lung Neoplasms D008207:Lymphatic Metastasis D008325:Mammary Neoplasms, Experimental D051379:Mice D008807:Mice, Inbred BALB C D055806:Microvessels D009368:Neoplasm Transplantation D034741:RNA, Small Interfering D047368:Tumor Burden D042582:Vascular Endothelial Growth Factor C D042643:Vascular Endothelial Growth Factor D
siRNA VEGF-C VEGF-D metastasis mammary cancer