Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA

  • Authors:
    • Rong-Xin Chen
    • Yun-Hong Xia
    • Tong-Chun Xue
    • Hong Zhang
    • Sheng-Long Ye
  • View Affiliations

  • Published online on: December 21, 2010     https://doi.org/10.3892/or.2010.1116
  • Pages: 803-808
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Abstract

Osteopontin (OPN) has an important role in hepatocellular carcinoma (HCC) progression and metastasis. This study was to investigate the therapeutic potential of inhibition of OPN expression. A 2'-O-methoxyethylribose-modified phosphorothioate antisense oligonucleotides (ASO) was used to knock-down OPN expression in the human metastatic HCC cell line HCCLM6 and in nude mice orthotopically implanted with HCCLM6 showing highly spontaneous lung metastasis. Furthermore, we assessed the metastatic potential of HCCLM6 cells in vitro and in vivo after ASO treatment. Treatment of HCCLM6 cells with OPN ASO inhibited OPN mRNA expression in a dose- and time-dependent manner, whereas the control oligonucleotides had no effect. OPN ASO significantly suppressed migration and invasion of HCCLM6 cells in vitro. Specific suppression of OPN also inhibited matrix metalloproteinase 2 (MMP-2) and urokinase-type plasminogen activator (uPA) expression in HCCLM6 cells. In mice bearing orthotopical xenografts with HCCLM6, OPN inhibition following therapeutic treatment with OPN ASO significantly decreased lung metastases although tumor weight did not appear to be reduced. These findings suggest that OPN-targeted therapy may be a promising strategy for the treatment of HCC metastases.

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March 2011
Volume 25 Issue 3

Print ISSN: 1021-335X
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Copy and paste a formatted citation
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Spandidos Publications style
Chen R, Xia Y, Xue T, Zhang H and Ye S: Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA. Oncol Rep 25: 803-808, 2011.
APA
Chen, R., Xia, Y., Xue, T., Zhang, H., & Ye, S. (2011). Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA. Oncology Reports, 25, 803-808. https://doi.org/10.3892/or.2010.1116
MLA
Chen, R., Xia, Y., Xue, T., Zhang, H., Ye, S."Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA". Oncology Reports 25.3 (2011): 803-808.
Chicago
Chen, R., Xia, Y., Xue, T., Zhang, H., Ye, S."Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA". Oncology Reports 25, no. 3 (2011): 803-808. https://doi.org/10.3892/or.2010.1116