کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8305055 1538423 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fsn0503h antibody-mediated blockade of cathepsin S as a potential therapeutic strategy for the treatment of solid tumors
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Fsn0503h antibody-mediated blockade of cathepsin S as a potential therapeutic strategy for the treatment of solid tumors
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 108, January 2015, Pages 101-107
نویسندگان
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