Fas-dependent tissue turnover is implicated in tumor cell clearance

The apoptosis-inducing Fas receptor has been shown to be down-regulated in various types of tumors, while its ligand (FasL) appears to be frequently u p-regulated. Here we provide evidence that there is a strong selective pres sure in vivo against Fas-expressing, tumorigenic NIH3T3 cells, favoring sur vival, proliferation and eventually tumor formation by Fas-negative tells. Importantly, re-expression of Fas in these cells results in either the comp lete abolishment of tumor development, or in a significant extenuation of t he latency period of tumor outgrowth. In addition, we found that environmen tal conditions which prevail during tumorigenesis, such as limiting amounts of survival factors and the lack of cell adhesion, are markedly sensitizin g tumor cells to Fas-mediated suicide. Our data suggest that in addition to T cell-mediated immune responses, mechanisms of Fas-dependent tissue turno ver are also centrally implicated in tumor cell clearance.