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

Abstract

We have previously reported that the expression of matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase (MT1-MMP) and beta1 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 alpha3beta1 (VLA-3), integrin alpha5beta1 (VLA-5) on the tumor surface, respectively.

• Authors: Yasunori Tsuchiya, Shigeaki Sawada, Kazuhiro Tsukada, Ikuo Saiki
• Journal: International journal of oncology (Int J Oncol) Vol. 20 Issue 2 Pg. 319-24 (Feb 2002) ISSN: 1019-6439 [Print] Greece
• PMID: 11788895 (Publication Type: Journal Article)

Chemical References

• Matrix Metalloproteinase Inhibitors
• Oligopeptides
• arginyl-glycyl-aspartic acid
• Matrix Metalloproteinases

Topics

• Animals
• Carcinoma, Hepatocellular (drug therapy, enzymology, pathology)
• Cell Adhesion (drug effects)
• Cell Death (drug effects)
• Cell Division (drug effects)
• Disease Models, Animal
• Electrophoresis, Polyacrylamide Gel
• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinases (metabolism)
• Mice
• Neoplasm Invasiveness
• Neoplasm Metastasis (drug therapy)
• Neoplasm Transplantation
• Oligopeptides (therapeutic use, toxicity)
• Tumor Cells, Cultured