Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells.
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.
Matthews
E
E
Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
Yang
T
T
Janulis
L
L
Goodwin
S
S
Kundu
S D
SD
Karpus
W J
WJ
Lee
C
C
D000818:Animals; D002455:Cell Division / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D020319:Oligodeoxyribonucleotides, Antisense; D016212:Transforming Growth Factor beta; D013936:Thymidine