Short hairpin RNA targeting of fibroblast activation protein inhibits tumor growth and improves the tumor microenvironment in a mouse model |
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| Authors: | Fan Cai Zhiyong Li Chunting Wang Shuang Xian Guangchao Xu Feng Peng Yuquan Wei You Lu |
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| Institution: | 1.Department of Thoracic Oncology of Cancer Centre and State Key Laboratory of Biotherapy, China;2.State Key Laboratory, Biotherapy and Cancer Centre, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China |
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| 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. BMB Reports 2013; 46(5): 252-257] |
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| Keywords: | Angiogenesis Breast cancer Fibroblast activation protein RNA interference Tumor microenvironment |
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