References

prostate, followed by epithelial neoplasia, and a similar process was observed in the forestomach. These findings suggest the existence of a TGF-β–induced signaling pathway that is initiated in the stroma and terminates, either directly or indirectly, in epithelial cells. That TGF-β indirectly pro-motes tumors by stimulating stromal reac-tivity and fibrosis is well established (17), but the fascinating discovery of Bhowmick et al. is that TGF-β signaling can act as an indirect tumor suppressor. Moreover, the fact that loss of TβRII in stromal fibro-blasts leads so quickly and so inexorably to epithelial carcinoma provides a clear coun-terexample to the assumption that muta-tions in epithelial cells are the required ini-tiating factors for carcinoma. Thus, far from being a mere “landscaper, ” the tissue microenvironment is a powerful regulator of tumor induction as well as tumor sup-pression—a role that clearly merits not on-ly further exploration, but also respect