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KMID : 0624620130460050252
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BMB Reports
2013 Volume.46 No. 5 p.252 ~ p.257
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Short hairpin RNA targeting of fibroblast activation protein inhibits tumor growth and improves the tumor microenvironment in a mouse model
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Cai Fan
Li Zhiyong
Wang Chunting
Xian Shuang
Xu Guangchao
Peng Feng
Wei Yuquan
Lu You
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Abstract
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Fibroblast activation protein (FAP) is a specific serine protease expressed in tumor stroma proven to be a stimulatory factor in the progression of some cancers. The purpose of this study was to investigate the effects of FAP knockdown on tumor growth and the tumor microenvironment. Mice bearing 4T1 subcutaneous tumors were treated with liposome-shRNA complexes targeting FAP. Tumor volumes and weights were monitored, and FAP, collagen, microvessel density (MVD), and apoptosis were measured. Our studies showed that shRNA targeting of FAP in murine breast cancer reduces FAP expression, inhibits tumor growth, promotes collagen accumulation (38%), and suppresses angiogenesis (71.7%), as well as promoting apoptosis (by threefold). We suggest that FAP plays a role in tumor growth and in altering the tumor microenvironment. Targeting FAP may therefore represent a supplementary therapy for breast cancer.
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KEYWORD
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Angiogenesis, Breast cancer, Fibroblast activation protein, RNA interference, Tumor microenvironment
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