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

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-β1. An expression construct containing a DNA sequence in an antisense orientation to TGF-β1 (TGF-β1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-β1 reduced from 70 to10 pg per 2 × 104cells and the rate of in vitro3H-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≤ 0.05) for cells transfected with TGF-β1 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-β1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-β1 is down-regulated. © 2000 Cancer Research Campaign