FAP is a type II integral membrane serine protease expressed on the surface of carcinoma-associated fibroblasts (CAFs) in the stroma of greater than 90% of solid tumors examined, but not on adjacent normal tissues. FAP expression has also been observed on activated fibroblasts in some soft tissue sarcomas and at sites of active tissue remodeling, including areas of wound healing, rheumatoid arthritis, and chronic fibrosis. Mesenchymal stem cells (MSCs), which can give rise to CAFs, and tumor-associated macrophages (TAMs) have also been shown to express FAP.. Both of these cell types have significant immunomodulatory properties that may play critical roles in tumor progression. This is supported by studies in which conditional knockout of FAP-expressing cells using diphtheria toxin restored immunological control of cancer growth in a genetically-engineered mouse model of pancreatic cancer.
Brennen WN, Rosen DM, Chaux A, Netto GJ, Isaacs JT, Denmeade SR. Pharmacokinetics and Toxicology of a Fibroblast Activation Protein (FAP)-activated Prodrug in Murine Xenograft Models of Human Cancer. The Prostate. 2014;74(13):1308-1319.