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The University of Western Australia Department of Medicine, Queen Elizabeth II Medical Centre, Verdum Street, Nedlands, 6008 Perth, Western Australia, Australia [A. L. M., B. W. S. R., B. S.], and the Transplantation Biology Unit, Queensland Institute of Medical Research, 300 Herston Road, 4006 Herston, Queensland, Australia [D. R. F.]
Transforming growth factor ß (TGF-ß) is a potent growth-regulatory and immunomodulatory cytokine that exerts a diverse range of effects on many types of cells. High levels of TGF-ß are produced by several human and mouse malignant mesothelioma (MM) cell lines, and it is known to act as a growth factor for these cells. Antisense oligonucleotides (ODNs), targeted against specific TGF-ß mRNA, were used to block TGF-ß production from MM cells in vitro and in vivo.
TGF-ß antisense ODNs were encapsulated in liposomes and transfected into MM cells or delivered intratumorally. TGF-ß2 mRNA levels, assessed by semiquantitative PCR, and TGF-ß2 protein secretion were reduced after TGF-ß2 antisense ODN transfection. MM cell proliferation, assessed by tritiated thymidine uptake, was specifically inhibited by both TGF-ß1- and TGF-ß2-specific antisense ODNs. In vivo administration of TGF-ß2 antisense ODNs, delivered locally, reduced tumor growth. These data show that the blockade of TGF-ß2 within this tumor reduces tumor growth and raises the possibility that TGF-ß2 antisense ODNs may be useful as a therapy for this disease.
1 Supported by the National Health and Medical Research Council of Australia and the Medical Research Fund of Western Australia.
2 To whom requests for reprints should be addressed. Phone: 061-8-9-346-3259; Fax: 061-8-9-346-2816; E-mail: amarzo@uniwa.uwa.edu.au.
Received 12/13/96. Accepted 5/29/97.
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