title: Short hairpin RNA targeting of fibroblast activation protein inhibits tumor growth and improves the tumor microenvironment in a mouse model.
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.
authors.affiliation: Department of Thoracic Oncology of Cancer Centre and State Key Laboratory of Biotherapy.
authors.forename: Fan
authors.initials: F
authors.lastname: Cai
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Li
authors.forename: Chunting
authors.initials: C
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Xian
authors.forename: Guangchao
authors.initials: G
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Peng
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: You
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000235:genetics; D059016:Tumor Microenvironment / Q000187:drug effects; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha