Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs

Keane, Fiona M., Yao, Tsun-Wen, Seelk, Stefanie, Gall, Margaret G., Chowdhury, Sumaiya, Poplawski, Sarah E., Lai, Jack H., Li, Youhua, Wu, Wengen, Farrell, Penny, Vieira de Ribeiro, Ana Julia, Osborne, Brenna, Yu, Denise M. T., Seth, Devanshi, Rahman, Khairunnessa, Haber, Paul, Topaloglu, A. Kemal, Wang, Chuanmin, Thomson,Sally, Hennessy, Annemarie, Prins, John, Twigg, Stephen M., McLennan, Susan V., McCaughan, Geoffrey W., Bachovchin, William W. and Gorrell, Mark D. (2014) Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs. FEBS Open Bio, 4 43-54. doi:10.1016/j.fob.2013.12.001

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Author Keane, Fiona M.
Yao, Tsun-Wen
Seelk, Stefanie
Gall, Margaret G.
Chowdhury, Sumaiya
Poplawski, Sarah E.
Lai, Jack H.
Li, Youhua
Wu, Wengen
Farrell, Penny
Vieira de Ribeiro, Ana Julia
Osborne, Brenna
Yu, Denise M. T.
Seth, Devanshi
Rahman, Khairunnessa
Haber, Paul
Topaloglu, A. Kemal
Wang, Chuanmin
Hennessy, Annemarie
Prins, John
Twigg, Stephen M.
McLennan, Susan V.
McCaughan, Geoffrey W.
Bachovchin, William W.
Gorrell, Mark D.
Title Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs
Journal name FEBS Open Bio   Check publisher's open access policy
ISSN 2211-5463
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.fob.2013.12.001
Open Access Status DOI
Volume 4
Start page 43
End page 54
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
Abstract The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ~20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.
Keyword Biomarker
Dipeptidyl peptidase
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 512282
R01 CA163930-01A1
Institutional Status UQ
Additional Notes Published online 8 December 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2014 Collection
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Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
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