Controlled release of TGF-β₁ impedes rat colon carcinogenesis in vivo

Transforming growth factor β₁ (TGF-β₁) is a cytokine known to play a key role in the control of cell growth. TGF-β₁ potently inhibits the proliferation of human and rodent-derived epithelial cells. Colonic precancerous and moderately differentiated cancer cells are responsive to TGF-β₁, whereas malignant colon cancer cells are resistant to the inhibitory action of the cytokine. These observations have been derived exclusively from in vitro studies. Therefore, the main aim of our study was to determine whether TGF-β₁ exerts a growth-restraining action on colon carcinogenesis in vivo. TGF-β₁ was sequestered into ethylene acetate copolymer matrices and 'loaded' preparations were implanted intraperitoneally (i.p.) in rats. One week later, the animals were treated with dimethylhydrazine (DMH), a colon procarcinogen. Empty matrices devoid of TGF- β₁ but containing bovine serum albumin (BSA) carrier served as the appropriate control preparations. The number of aberrant crypt loci (ACF), considered to be preneoplastic lesions of the colon, was scored. Tumor formation and size were assessed at the appropriate times. TGF-β₁ released in a sustained manner from copolymer matrices: (i) markedly inhibited colonic ACF formation and the number of aberrant crypts and (ii) significantly reduced colonic tumor formation and size.