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: Fan Cai, Zhiyong Li, Chunting Wang, Shuang Xian, Guangchao Xu, Feng Peng, Yuquan Wei, You Lu
• Journal: BMB reports (BMB Rep) Vol. 46 Issue 5 Pg. 252-7 (May 2013) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 23710635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• RNA, Small Interfering
• Endopeptidases
• Serine Endopeptidases
• fibroblast activation protein alpha
• Gelatinases

Topics

• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (therapy)
• Cell Line, Tumor
• Disease Models, Animal
• Drug Delivery Systems
• Endopeptidases
• Female
• Gelatinases (antagonists & inhibitors, genetics)
• Gene Knockdown Techniques
• Humans
• Immunohistochemistry
• Membrane Proteins (antagonists & inhibitors, genetics)
• Mice
• RNA, Small Interfering (pharmacology)
• Serine Endopeptidases (genetics)
• Tumor Microenvironment (drug effects)