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 u nderstood. 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 a gainst either TGF-beta 1 or -beta 2 cross-inhibited both TGF-beta 1 an d -beta 2 expression, (c) inhibition of TGF-beta expression reduced th e anchorage-independent growth of MM cells in vitro and the tumorigeni city of MM cells in vivo, and (d) inhibition of TGF-beta expression le d to increased T lymphocyte infiltration into tumors. The data suggest that TGF-beta has multiple tumor-enhancing effects in MM.