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 proteaseexpressed in tumor stroma proven to be a stimulatory factor inthe progression of some cancers. The purpose of this studywas to investigate the effects of FAP knockdown on tumorgrowth and the tumor microenvironment. Mice bearing 4T1subcutaneous tumors were treated with liposome-shRNAcomplexes targeting FAP. Tumor volumes and weights weremonitored, and FAP, collagen, microvessel density (MVD),and apoptosis were measured. Our studies showed thatshRNA targeting of FAP in murine breast cancer reduces FAPexpression, inhibits tumor growth, promotes collagenaccumulation (38%), and suppresses angiogenesis (71.7%), aswell as promoting apoptosis (by threefold). We suggest thatFAP plays a role in tumor growth and in altering the tumormicroenvironment. Targeting FAP may therefore represent asupplementary therapy for breast cancer. [BMB Reports 2013;46(5): 252-257]

Keywords

• Angiogenesis
• Breast cancer
• Fibroblast activation protein
• RNA interference
• Tumor microenvironment