1. Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice
- Author
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Volker Gerke, Carsten Müller-Tidow, Wolfgang E. Berdel, Ruediger Liersch, Sven Diederichs, Biilent Sargin, Rolf M. Mesters, Marc Hotfilder, Antje Hascher, Etmar Bulk, Josef Vormoor, and Hubert Serve
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Angiogenesis ,Mice, SCID ,Adenocarcinoma ,Transfection ,Metastasis ,Small hairpin RNA ,Mice ,RNA interference ,Mice, Inbred NOD ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Adjuvant therapy ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,RNA, Small Interfering ,Lung cancer ,Neovascularization, Pathologic ,business.industry ,Calcium-Binding Proteins ,Cancer ,Genetic Therapy ,medicine.disease ,Primary tumor ,Xenograft Model Antitumor Assays ,Neoplasm Proteins ,Oncology ,Cancer research ,RNA Interference ,business - Abstract
Development of distant metastasis is the major reason for cancer-related deaths worldwide. Adjuvant therapy approaches after local therapies are most effective when specific targets are inhibited. Recently, we identified S100P overexpression as a strong predictor for metastasis development in early-stage non–small cell lung cancer (NSCLC) patients. Here, we show that S100P overexpression increased angiogenesis in and metastasis formation from s.c. xenotransplants of NSCLC cells. Plasmid-derived short hairpin RNAs (shRNA) were developed as specific adjuvant therapy. I.v. injected shRNA against S100P significantly decreased S100P protein expression in xenograft tumors and inhibited tumor angiogenesis in vivo. Metastasis formation 8 weeks after primary tumor resection was significantly reduced. Lung metastases developed in 31% of mice treated with S100P-targeting shRNAs compared with 64% in control shRNA–treated mice (P < 0.05). These findings suggest that RNA interference–based therapy approaches can be highly effective in the adjuvant setting. [Cancer Res 2008;68(6):1896–904]
- Published
- 2008