DIFFERENTIATION RESPONSES OF EMBRYONIC ENDOTHELIUM TO LEUKEMIA INHIBITORY FACTOR

The IEM cell line is a murine embryonic endothelial cell line that res ponds to combinations of basic fibro blast growth factor (bFGF) and le ukemia inhibitory factor (LIF) by undergoing proliferation and vasculo genic differentiation in vitro and in vivo. Exposure to LIF and bFGF i n vitro permits the IEM cells to specifically chimerize endothelium in vivo and recapitulate normal endothelial development after blastocyst injection. We report here that unmanipulated IEM cells form vascular neoplasias when injected into immunodeficient nude mice. Examination o f IEM neoplasia following exposure in vitro to bFGF and LIF before inj ection into nude mice profoundly reduced or completely suppressed the neoplastic growth of IEM cells. Furthermore, this suppression was obse rved by treatment with LIF alone, while bFGF treatment did not signifi cantly alter IEM neoplasia and did not modify the LIF-mediated suppres sion. Characterization of the IEM responses to LIF revealed that the L IF suppression of IEM neoplasia depended on how long the cells were ex posed to LIF in vitro. The IEM cell response to LIF was associated wit h the specific activation of the transcription factor Stat3. Stat1 act ivation could not be detected in response to LIE, although it is expre ssed in IEM cells. Our results demonstrate that the LIF-induced differ entiation of IEM cells involves suppression of IEM-derived neoplasia a nd is associated with the specific activation of Stat3. (C) 1998 Acade mic Press.