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http://dx.doi.org/10.5483/BMBRep.2013.46.5.172

Short hairpin RNA targeting of fibroblast activation protein inhibits tumor growth and improves the tumor microenvironment in a mouse model  

Cai, Fan (Department of Thoracic Oncology of Cancer Centre and State Key Laboratory of Biotherapy)
Li, Zhiyong (State Key Laboratory, Biotherapy and Cancer Centre, West China Hospital, Sichuan University)
Wang, Chunting (State Key Laboratory, Biotherapy and Cancer Centre, West China Hospital, Sichuan University)
Xian, Shuang (Department of Thoracic Oncology of Cancer Centre and State Key Laboratory of Biotherapy)
Xu, Guangchao (State Key Laboratory, Biotherapy and Cancer Centre, West China Hospital, Sichuan University)
Peng, Feng (Department of Thoracic Oncology of Cancer Centre and State Key Laboratory of Biotherapy)
Wei, Yuquan (State Key Laboratory, Biotherapy and Cancer Centre, West China Hospital, Sichuan University)
Lu, You (Department of Thoracic Oncology of Cancer Centre and State Key Laboratory of Biotherapy)
Publication Information
BMB Reports / v.46, no.5, 2013 , pp. 252-257 More about this Journal
Abstract
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.
Keywords
Angiogenesis; Breast cancer; Fibroblast activation protein; RNA interference; Tumor microenvironment;
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