Ribozyme targeting of the growth factor pleiotrophin in established tumors: A gene therapy approach

  • Malerczyk C
  • Schulte A
  • Czubayko F
 et al. 
  • 11

    Readers

    Mendeley users who have this article in their library.
  • 13

    Citations

    Citations of this article.

Abstract

The growth and metastasis of solid tumors relies on the activities of polypeptide growth factors to recruit stromal tissue and expand the tumor mass. Pleiotrophin (PTN) is a secreted growth factor with angiogenic activity that has been found to contribute to the growth and metastasis of tumors including melanoma. Here, we present a gene therapy approach of targeting PTN in established tumors using ribozymes. Tetracycline-regulated ribozyme expression vectors were used to deplete conditionally PTN mRNA from melanoma xenograft tumors in vivo. We found that tetracycline-mediated initiation of ribozyme expression in established tumors reduced further tumor growth. Next, we generated synthetic anti-PTN ribozymes that inhibit PTN-dependent colony formation of cells in soft agar. Intraperitoneal administration of these synthetic ribozymes into nude mice inhibited growth of PTN-positive, subcutaneous melanoma. Furthermore, PTN released from the tumors into the circulation of mice was reduced after ribozyme treatment. These data show that ribozyme targeting of rate-limiting tumor growth factors could provide an efficient tool for cancer therapy and that the efficacy may be reflected in the reduction of the serum levels of the targeted protein, PTN.

Author-supplied keywords

  • Growth factor
  • Melanoma
  • Pleiotrophin
  • Ribozymes

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • C. Malerczyk

  • A. M. Schulte

  • F. Czubayko

  • L. Bellon

  • D. Macejak

  • A. T. Riegel

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free