Fibroblast Activation Protein (FAP) is an enzyme that breaks down other proteins. “In normal tissues, FAP is quiet and almost completely undetectable,” says scientist Nathaniel Brennen, Ph.D. “It only really shows up when your tissues need repair, like when you get an injury and your body needs to heal.” 

FAP also shows up, a recent Brady study has found, in the presence of inflammation or cancer in the prostate – and it is expressed at greater levels in aggressive prostate cancer. In this study, published in Pathology, senior investigators Brennen, Srinivasan Yegnasubramanian, M.D., Ph.D., Angelo De Marzo, M.D., Ph.D., and team used immunohistochemistry to analyze FAP’s expression in normal and malignant prostate tissues. 

“We found that FAP was largely absent in normal prostate tissue, but significantly elevated in areas of proliferative inflammatory atrophy (PIA), a potential precursor to cancer,” says Brennen. FAP was present in all of the prostate cancer samples they studied, “although expression levels varied widely within each tumor. Notably, higher-grade, advanced cancer contained more FAP, suggesting its potential role as an indicator of tumor aggressiveness.” 

The study, spearheaded by lead author, Fernanda Caramella-Pereira, M.D., also identified higher FAP levels in tissues rich in immune cells called M2 macrophages – suggesting FAP may recruit these cells as camouflage to shield the prostate cancer from attack by the immune system. 

The findings support the idea put forth many years ago by team members that PIA represents regions of cellular injury and remodeling in the prostate, in response to inflammation, that can serve as a hotbed for cancer cells to develop. “We believe FAP could be a promising potential target for molecular imaging and drug therapies in prostate cancer,” says Brennen. 

Other investigators on the study include Qizhi Zheng, Jessica Hicks, Sujayita Roy, Tracy Jones, Martin Pomper, Lizamma Antony, and Alan Meeker.