Fsn0503h antibody-mediated blockade of cathepsin S as a potential therapeutic strategy for the treatment of solid tumors.

Détails

ID Serval
serval:BIB_F3CD9CCD41B0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Fsn0503h antibody-mediated blockade of cathepsin S as a potential therapeutic strategy for the treatment of solid tumors.
Périodique
Biochimie
Auteur(s)
Vázquez R., Astorgues-Xerri L., Bekradda M., Gormley J., Buick R., Kerr P., Cvitkovic E., Raymond E., D'Incalci M., Frapolli R., Riveiro M.E.
ISSN
1638-6183 (Electronic)
ISSN-L
0300-9084
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
108
Pages
101-107
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.
Pubmed
Création de la notice
11/02/2015 13:03
Dernière modification de la notice
03/03/2018 22:43
Données d'usage