Down-regulation of TGF-β1 production restores immunogenicity in prostate cancer cells

被引:37
作者
Matthews, E. [1 ]
Yang, T. [1 ]
Janulis, L. [1 ]
Goodwin, S. [1 ]
Kundu, S. D. [1 ]
Karpus, W. J. [2 ]
Lee, C. [1 ]
机构
[1] Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA
[2] Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA
关键词
TGF-beta expression; rat prostate cancer; immunogenicity; tumour incidence; host-tumour interaction;
D O I
10.1054/bjoc.2000.1257
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-beta 1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta 1 (TGF-beta 1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta 1 reduced from 70 to 10 pg per 2 x 10(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 <= 0.05) for cells transfected with TGF-beta 1 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-beta 1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta 1 is down-regulated. (C) 2000 Cancer Research Campaign
引用
收藏
页码:519 / 525
页数:7
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