Title:Fibroblast Activation Protein in Remodeling Tissues
Volume: 12
Issue: 10
Author(s): M. Jacob, L. Chang and E. Pure
Affiliation:
Keywords:
Cancer, development, dipeptidyl peptidase, endopeptidase, extracellular matrix, fibroblast activation
protein, fibrosis, inflammation, matrix remodeling, tumor microenvironment, wound healing, carcinomas, proteolglycans, glycosaminoglycans, protease inhibitors
Abstract: Tissue remodeling is critical during development and wound healing. It also characterizes a number
of pathologic conditions, including chronic inflammation, fibrosis and cancer. It is well appreciated that reactive
stromal cells play critical roles in these settings. However, understanding of the mechanisms involved in the
differentiation of reactive stromal cells and their biologic activities has been hampered by the fact that they are
generated from diverse progenitors, and by their phenotypic and function heterogeneity. Furthermore,
molecular markers that are expressed by all reactive stromal cells and that distinguish them from all other cell
types have been lacking.
Fibroblast activation protein (FAP) is a serine protease that was originally discovered as a cell surface protein
expressed on astrocytomas and sarcomas. Over the last two decades, FAP has attracted increasing attention
as a selective marker of carcinoma-associated fibroblasts (CAFs) and more broadly, of activated fibroblasts in
tissues undergoing remodeling of their extracellular matrix (ECM) due to chronic inflammation, fibrosis or
wound healing. Herein we review the evidence that FAP is indeed a robust and selective marker for reactive
mesenchymal stromal cells associated with pathophysiologic tissue remodeling. We also review recent insights
obtained using FAP as a tool to define the relationship between subpopulations of reactive stromal cells in
various settings of tissue remodeling. Furthermore, we review recent genetic and pharmacologic data
indicating that FAP and FAP-expressing cells play important roles in such conditions. Finally, we discuss the
potential risks and therapeutic benefits of targeting FAP and FAP-expressing cells, as well as approaches to
do so.
