Document Detail

Fibroblast activation protein in remodeling tissues.
MedLine Citation:
PMID:  22834826     Owner:  NLM     Status:  MEDLINE    
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.
M Jacob; L Chang; E Puré
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current molecular medicine     Volume:  12     ISSN:  1875-5666     ISO Abbreviation:  Curr. Mol. Med.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-28     Completed Date:  2013-06-20     Revised Date:  2014-06-13    
Medline Journal Info:
Nlm Unique ID:  101093076     Medline TA:  Curr Mol Med     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1220-43     Citation Subset:  IM    
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MeSH Terms
Cell Transformation, Neoplastic / metabolism
Extracellular Matrix / metabolism
Fibroblasts / metabolism
Fibrosis / metabolism
Gelatinases / chemistry*,  metabolism*
Inflammation / metabolism
Membrane Proteins / chemistry*,  metabolism*
Mesenchymal Stromal Cells / metabolism*,  pathology
Neoplasms / metabolism
Serine Endopeptidases / chemistry*,  metabolism*
Tumor Markers, Biological / genetics,  metabolism
Tumor Microenvironment
Wound Healing / physiology
Reg. No./Substance:
0/Membrane Proteins; 0/Tumor Markers, Biological; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/fibroblast activation protein alpha; EC 3.4.24.-/Gelatinases

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