Inhibition and Promotion of Differentiated-Like Phenotype of a Human Lung Carcinoma in Athymic Mice by Natural and Recombinant Forms of Transforming Growth Factor-beta

Abstract

Both structurally related forms of transforming growth factor-β (TGF-β types I and II) are potent inhibitors of tumor cell growth in vitro and can also modulate the differentiation of some cells in culture. In this study, we describe the effects of natural and recombinant TGF-βs on the growth and differentiation of a xenograft of human lung adenocarcinoma A549 in male athymic BALB/c mice. Subcutaneous, peritumoral injection of both forms of TGF-β inhibited, in a dose-dependent manner, the growth of established human lung tumors. Histologically, tumors inhibited by TGF-β appeared more differentiated, as judged by reduced mitotic activity and a predominance of highly specialized mucusecreting goblet-like cell types. These findings suggest that TGF-βs can be useful in the development of novel, perhaps less cytotoxic, cancer therapeutic strategies. [J Natl Cancer Inst 81:1182–1185, 1989]