Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells

Br J Cancer. 2000 Aug;83(4):519-25. doi: 10.1054/bjoc.2000.1257.

Abstract

The objective of this study is to determine if a non-immunogenic Dunning's rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-beta1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta1 (TGF-beta1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta1 reduced from 70 to 10 pg per 2x10(4) cells and the rate of in vitro 3H-thymidine incorporation increased 3-5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P< or =0.05) for cells transfected with TGF-beta1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-beta1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta1 is down-regulated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Division / physiology
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Disease Progression
  • Down-Regulation
  • Male
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / metabolism*
  • Rats
  • Rats, Inbred Lew
  • Rats, Nude
  • Thymidine / metabolism
  • Transfection
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*
  • Tumor Cells, Cultured

Substances

  • DNA, Complementary
  • Oligodeoxyribonucleotides, Antisense
  • Transforming Growth Factor beta
  • Thymidine