Antisense phosphorothioate oligodeoxynucleic acid for CD10 suppresses liver metastasis of colorectal cancer

Pathobiology. 2009;76(5):267-73. doi: 10.1159/000228903. Epub 2009 Oct 2.

Abstract

CD10 expression is associated with metastases of colorectal cancer (CRC). In the present study, we examined association of CD10 with liver metastasis of CRC cells to clarify the therapeutic significance of CD10. CD10-positive human colon cancer cell line, HT29 cells showed inhibition of growth, invasion and colony formation by treatment with CD10 antisense S-oligodeoxynucleotide (S-ODN). In the mouse liver metastasis mode, CD10 antisense S-ODN-treated HT29 cells made less embedded cells in the liver than control HT29 cells. Number and size of metastatic foci in nude mice liver were reduced in CD10 antisense S-ODN-treated HT29 cells. Treatment with CD10 antisense S-ODN decreased phosphorylation of ERK1/2 and EGFR in HT29 cells. Intraperitoneal administration of liposome-capsulated CD10 antisense S-ODN inhibited establishment of liver metastasis and growth of established metastasis in nude mice. These findings suggest that CD10 is associated substantially with liver metastasis of CRC cells and might be a molecular target of CRC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / metabolism*
  • Liver Neoplasms, Experimental / secondary*
  • Mice
  • Mice, Nude
  • Neprilysin / metabolism*
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Phosphorothioate Oligonucleotides / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Oligodeoxyribonucleotides, Antisense
  • Phosphorothioate Oligonucleotides
  • Neprilysin