Paradis H, Arceci R J, Adams L C, Gendron R L
Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Exp Cell Res. 1998 Apr 10;240(1):7-15. doi: 10.1006/excr.1998.4006.
The IEM cell line is a murine embryonic endothelial cell line that responds to combinations of basic fibroblast growth factor (bFGF) and leukemia inhibitory factor (LIF) by undergoing proliferation and vasculogenic differentiation in vitro and in vivo. Exposure to LIF and bFGF in 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 of IEM neoplasia following exposure in vitro to bFGF and LIF before injection into nude mice profoundly reduced or completely suppressed the neoplastic growth of IEM cells. Furthermore, this suppression was observed by treatment with LIF alone, while bFGF treatment did not significantly alter IEM neoplasia and did not modify the LIF-mediated suppression. Characterization of the IEM responses to LIF revealed that the LIF suppression of IEM neoplasia depended on how long the cells were exposed to LIF in vitro. The IEM cell response to LIF was associated with the specific activation of the transcription factor Stat3. Stat1 activation could not be detected in response to LIF, although it is expressed in IEM cells. Our results demonstrate that the LIF-induced differentiation of IEM cells involves suppression of IEM-derived neoplasia and is associated with the specific activation of Stat3.
IEM细胞系是一种小鼠胚胎内皮细胞系，在体外和体内，它会对碱性成纤维细胞生长因子（bFGF）和白血病抑制因子（LIF）的组合作出反应，进行增殖和血管生成分化。在体外暴露于LIF和bFGF时，IEM细胞能够在体内特异性地与内皮细胞嵌合，并在囊胚注射后重现正常的内皮发育。我们在此报告，未经过处理的IEM细胞注射到免疫缺陷的裸鼠体内时会形成血管肿瘤。在将IEM细胞注射到裸鼠体内之前，先在体外将其暴露于bFGF和LIF，然后对IEM肿瘤进行检查，结果显示IEM细胞的肿瘤生长显著减少或完全受到抑制。此外，单独用LIF处理也能观察到这种抑制作用，而bFGF处理并没有显著改变IEM肿瘤，也没有改变LIF介导的抑制作用。对IEM对LIF反应的特征分析表明，LIF对IEM肿瘤的抑制作用取决于细胞在体外暴露于LIF的时间长短。IEM细胞对LIF的反应与转录因子Stat3的特异性激活有关。尽管IEM细胞中表达了Stat1，但未检测到其对LIF的激活反应。我们的结果表明，LIF诱导的IEM细胞分化涉及对IEM来源肿瘤的抑制，并与Stat3的特异性激活有关。
