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Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas
Burden R.E.2; Gormley J.A.2; Kuehn D.2; Ward C.2; Kwok H.F.2; Gazdoiu M.2; McClurg A.2; Jaquin T.J.2; Johnston J.A.2; Scott C.J.1; Olwill S.A.2
2012-02-01
Source PublicationBiochimie
ISSN03009084 61831638
Volume94Issue:2Pages:487-493
Abstract

Cathepsin S is a lysosomal cysteine protease implicated in tumourigenesis with key roles in invasion and angiogenesis. We have previously shown that the specific inhibition of Cathepsin S using a monoclonal antibody (Fsn0503) blocks colorectal carcinoma tumour growth and angiogenesis in vivo. We investigated whether Cathepsin S expression levels were affected by chemotherapy in human cancer cell lines by RT-PCR. Using colorectal xenograft models, we examined the therapeutic benefit of Cathepsin S inhibition using Fsn0503 in combination with a metronomic dosing regimen of CPT-11. We analysed the effects of the combination therapy on tumour progression and on tumour vascularisation by immunohistochemical staining of tumours. Cathepsin S expression levels are upregulated in HCT116, LoVo, Colo205 cell lines and HUVECs after exposure to CPT-11 in vitro. The administration of Fsn0503 in combination with CPT-11 significantly attenuated tumour growth in comparison to CPT-11 alone in colorectal HCT116 xenograft models. Furthermore, analysis of tumour vascularisation revealed that this was also significantly disrupted by the combination treatment. These results show that the combination of Cathepsin S inhibition with CPT-11 enhances the therapeutic effect of the chemotherapy. This rationale may have clinical application in the treatment of colorectal cancer upon further evaluation. © 2011 Elsevier Masson SAS. All rights reserved.

KeywordAngiogenesis Cathepsin Chemotherapy Invasion
DOI10.1016/j.biochi.2011.08.017
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000300270900024
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Cited Times [WOS]:28   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Queen's University Belfast
2.Fusion Antibodies plc
Recommended Citation
GB/T 7714
Burden R.E.,Gormley J.A.,Kuehn D.,et al. Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas[J]. Biochimie,2012,94(2):487-493.
APA Burden R.E..,Gormley J.A..,Kuehn D..,Ward C..,Kwok H.F..,...&Olwill S.A..(2012).Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas.Biochimie,94(2),487-493.
MLA Burden R.E.,et al."Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas".Biochimie 94.2(2012):487-493.
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