Titre
Fsn0503h antibody-mediated blockade of cathepsin S as a potential therapeutic strategy for the treatment of solid tumors.
Type
article
Institution
Externe
Périodique
Auteur(s)
Vázquez, R.
Auteure/Auteur
Astorgues-Xerri, L.
Auteure/Auteur
Bekradda, M.
Auteure/Auteur
Gormley, J.
Auteure/Auteur
Buick, R.
Auteure/Auteur
Kerr, P.
Auteure/Auteur
Cvitkovic, E.
Auteure/Auteur
Raymond, E.
Auteure/Auteur
D'Incalci, M.
Auteure/Auteur
Frapolli, R.
Auteure/Auteur
Riveiro, M.E.
Auteure/Auteur
Liens vers les personnes
ISSN
1638-6183
Statut éditorial
Publié
Date de publication
2015
Volume
108
Première page
101
Dernière page/numéro d’article
107
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Degradation of extracellular matrix components is a key step in tumor progression, facilitating invasion, angiogenesis, and metastasis. The lysosomal cysteine protease cathepsin S (Cat-S) is a prominent player in this process. We evaluated the antitumor activity of Fsn0503h, the first Cat-S-antagonistic humanized monoclonal antibody, in a panel of cancer cell lines and in human colon carcinoma xenografts. Cat-S was expressed in 11 out of 36 solid tumor-derived cell lines. Fsn0503h significantly reduced the invasive capacity of all Cat-S-expressing cell lines in vitro. This was confirmed by the Cat-S small-molecule inhibitor Z-FL-COCHO, validating the importance of this protease in tumor cell invasiveness. Interestingly, Fsn0503h displayed antiproliferative effects in Cat-S positive and some Cat-S-negative cell lines. We provide the first demonstration of in vivo activity of Fsn0503h against a colorectal tumor xenograft model, with a 10 mg/kg three times a week intravenous schedule being optimal. In conclusion, Fsn0503h not only inhibited the invasiveness of cancer cells in vitro, but also exerted antitumor effects both in vitro and in vivo. These findings validate Cat-S as a therapeutic target, and support the development of Fsn0503h for the therapy of solid tumors.
PID Serval
serval:BIB_F3CD9CCD41B0
PMID
Date de création
2015-02-11T11:03:33.630Z
Date de création dans IRIS
2025-05-21T06:52:10Z