title: Fibroblast activation protein-α: a key modulator of the microenvironment in multiple pathologies.
abstract: Fibroblast activation protein-α (FAP) is a serine protease that can provide target specificity to therapeutic agents because in adults its expression is restricted to pathologic sites, including cancer, fibrosis, arthritis, wounding, or inflammation. It is not expressed in most normal tissues. The majority of FAP is expressed by activated fibroblasts responding to the pathologic situations. FAP is typically found as a type II transmembrane protein physically attached to cells and with the bulk of the protein, including the catalytic domain, exposed to the extracellular space and accessible to small molecules. In this chapter, we review the structure, substrate specificities, signaling functions, and current design of FAP inhibitors. Evidence indicating the presence of FAP in multiple cancers, arthritis, fibrosis, keloids, and other pathologies is described and indicates possible roles for FAP in facilitating cell invasion and growth. Separate sections are devoted to the role of FAP in coordinating the stromal response to cancer, including a role in angiogenesis and a potential role in modulation of the antitumor immune response. Finally studies attempting to demonstrate the clinical potential of FAP are discussed, as well as some novel applications employing FAP in therapy or diagnosis. Throughout this review, effort is made to highlight areas where information is lacking and to highlight important questions that require further investigation.
authors.affiliation: Department of Pathology and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelly
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Avis E
authors.initials: AE
authors.lastname: Simms
authors.forename: Anna
authors.initials: A
authors.lastname: Mazur
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000187:drug effects; D004194:Disease; D010450:Endopeptidases; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D000099167:Fibroblast Activation Protein Alpha