Transforming growth factor-beta: antisense RNA-mediated inhibition affects anchorage-independent growth, tumorigenicity and tumor-infiltrating T-cells in malignant mesothelioma.
Transforming growth factor-beta (TGF-beta) is produced by a number of tumor cell types including human malignant mesothelioma (MM), but its role as a direct or indirect factor in tumorigenesis is incompletely understood. We have investigated the expression of TGF-beta isoforms by human and murine MM cells and have analysed the effects of inducible antisense RNA-mediated inhibition of TGF-beta expression on murine MM in vitro and in vivo. The results showed that (a) TGF-beta 1 and -beta 2 were produced by both human and mouse MM cells, (b) antisense RNA against either TGF-beta 1 or -beta 2 cross-inhibited both TGF-beta 1 and -beta 2 expression, (c) inhibition of TGF-beta expression reduced the anchorage-independent growth of MM cells in vitro and the tumorigenicity of MM cells in vivo, and (d) inhibition of TGF-beta expression led to increased T lymphocyte infiltration into tumors. The data suggest that TGF-beta has multiple tumor-enhancing effects in MM.
University of Western Australia, Department of Medicine, QEII Medical Centre, Nedlands.
D R
DR
Fitzpatrick
H
H
Bielefeldt-Ohmann
R P
RP
Himbeck
A G
AG
Jarnicki
A L
AL
Marzo
B W
BW
Robinson
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008654:Mesothelioma / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000473:pathology
D017931:DNA Primers; D016372:RNA, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta