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The Potential of Osteopontin as a Therapeutic Target for Human Colorectal Cancer.
MedLine Citation:
PMID:  21318445     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Osteopontin (OPN), a phosphorylated glycoprotein, is involved in tumor progression and metastasis. Previously, we have reported that high OPN mRNA expression level possessed clinicopathological or prognostic significance in human colorectal cancer (CRC). The aim of this study is to investigate whether OPN can serve as a novel molecular target for CRC therapy. MATERIAL AND METHODS: Western Blot assay was performed to detect the expression of OPN protein in 18 CRC and corresponding nontumor colon tissue samples. RNA interference (RNAi) was employed to knockdown endogenous OPN expression in CRC cell line (LoVo). MTT, colony formation, and tumorigenicity assays were performed to analyze the effect of OPN downregulation on the in vitro and in vivo proliferation of CRC cells. Wound healing and Matrigel invasion assays were performed to analyze the effect of OPN downregulation on migration and invasion of CRC cells. A clonogenic cell survival assay after radiation was performed to analyze the effect of OPN downregulation on the radiosensitivity of CRC cells. RESULTS: The relative level of OPN protein expression in CRC tissues was significantly higher than that in corresponding nontumor colon tissues (P < 0.05). We found that RNAi-mediated OPN downregulation could inhibit not only in vitro proliferation but also in vivo tumorigenicity of CRC cells. In addition, OPN downregulation could suppress in vitro invasion capacity and enhance in vitro radiosensitivity of CRC cells, which might be associated with decreased levels of MMP-2 and -9 expression. CONCLUSION: RNAi-targeting OPN could inhibit proliferation, invasion and enhance radiosensitivity of human CRC cells. Therefore, OPN could serve as a novel molecular target for gene therapy of CRC.
Authors:
Wang Likui; Wang Hong; Zhang Shuwen; You Yuangang; Wen Yan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-12
Journal Detail:
Title:  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract     Volume:  -     ISSN:  1873-4626     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9706084     Medline TA:  J Gastrointest Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Infection, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing, 100050, People's Republic of China, kui_li2008@yahoo.com.cn.
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