A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma

  • Authors:
    • Yasunori Tsuchiya
    • Shigeaki Sawada
    • Kazuhiro Tsukada
    • Ikuo Saiki
  • View Affiliations

  • Published online on: February 1, 2002     https://doi.org/10.3892/ijo.20.2.319
  • Pages: 319-324
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Abstract

We have previously reported that the expression of matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase (MT1-MMP) and β1 integrins in murine hepatocellular carcinoma (HCC) was associated with the occurrence of intrahepatic metastasis, which is considered to be a major modality in recurrence. Here we show that intravenous administration of synthetic RGD pseudo-peptide (FC-336) inhibited intrahepatic metastasis produced by orthotopic implantation of a fragment of murine HCC (CBO140C12) tumor as compared with control administration of vehicle (p<0.05), but did not affect the growth of the implanted tumor. To further analyze the anti-metastatic effect of FC-336, we investigated the effects of FC-336 on tumor growth, adhesion and invasion in vitro. FC-336 at non-cytotoxic concentration of less than 5 mg/ml effectively inhibited the adhesion and invasion of CBO140C12 cells (p<0.05). We also used zymography to examine the effect of FC-336 on the gelatinolysis of MMPs produced by CBO140C12 cells. FC-336 inhibited the degradation of the gelatin substrate by MMP-9 in a concentration-dependent manner. These results strongly suggest that intrahepatic metastasis of CBO140C12 tumors is partly due to the marked invasive and adhesive abilities of tumor cells mediated by expression of MMP-9 and integrin α3β1 (VLA-3), integrin α5β1 (VLA-5) on the tumor surface, respectively.

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February 2002
Volume 20 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tsuchiya Y, Sawada S, Tsukada K and Saiki I: A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma. Int J Oncol 20: 319-324, 2002
APA
Tsuchiya, Y., Sawada, S., Tsukada, K., & Saiki, I. (2002). A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma. International Journal of Oncology, 20, 319-324. https://doi.org/10.3892/ijo.20.2.319
MLA
Tsuchiya, Y., Sawada, S., Tsukada, K., Saiki, I."A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma". International Journal of Oncology 20.2 (2002): 319-324.
Chicago
Tsuchiya, Y., Sawada, S., Tsukada, K., Saiki, I."A new pseudo-peptide of Arg-Gly-Asp (RGD) inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma". International Journal of Oncology 20, no. 2 (2002): 319-324. https://doi.org/10.3892/ijo.20.2.319