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The Potential of Osteopontin as a Therapeutic Target for Human Colorectal Cancer

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

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.

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Acknowledgments

This work was supported by the Project Sponsored by the Scientific Research Foundation for the Beijing Returned Overseas.

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Authors and Affiliations

  1. Department of Infection, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing, 100050, People’s Republic of China

    Wang Likui, Wang Hong, Zhang Shuwen & Wen Yan

  2. Beijing Tropical Medicine Institute, Beijing Friendship Hospital, Beijing, People’s Republic of China

    You Yuangang

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  1. Wang Likui
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  2. Wang Hong
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  3. Zhang Shuwen
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  4. You Yuangang
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  5. Wen Yan
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Correspondence to Wang Likui.

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Likui, W., Hong, W., Shuwen, Z. et al. The Potential of Osteopontin as a Therapeutic Target for Human Colorectal Cancer. J Gastrointest Surg 15, 652–659 (2011). https://doi.org/10.1007/s11605-011-1445-6

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  • DOI: https://doi.org/10.1007/s11605-011-1445-6

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