Rothermel Terri A, Engelhardt Britta, Sheibani Nader
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin 53792-4673, USA.
J Cell Physiol. 2005 Jan;202(1):230-9. doi: 10.1002/jcp.20114.
Wild-type mouse brain endothelial (bEND) cells transformed with the polyoma virus middle-T proliferate rapidly in culture and form hemangiomas in mice. These cells express high levels of platelet/endothelial cell adhesion molecule-1 (PECAM-1), a molecule shown to be important during hemangioma formation. In this study, we have examined the ability of polyoma virus middle-T-transformed mouse bEND cells prepared from PECAM-1-/- mice to proliferate in culture and form hemangiomas in mice. We show that these cells express a number of endothelial cell markers and share a similar morphology with PECAM-1+/+ bEND cells. PECAM-1-/- bEND cells exhibit a limited ability to form tubes in Matrigel and rapidly form hemangioma when injected into nude mice, very similar to PECAM-1+/+ bEND cells. These cells, however, have increased proliferation, slower migration, altered endothelial cell adhesion molecule expression, and are less adherent when compared to PECAM-1+/+ bEND cells. Therefore, lack of PECAM-1 expression impacts polyoma middle-T-transformed endothelial cell proliferative, adhesive, and migratory properties without impacting their ability to rapidly form hemangiomas in mice or poorly organize to capillary-like structures in Matrigel.
用多瘤病毒中T抗原转化的野生型小鼠脑内皮(bEND)细胞在培养中迅速增殖,并在小鼠体内形成血管瘤。这些细胞高水平表达血小板/内皮细胞黏附分子-1(PECAM-1),该分子在血管瘤形成过程中显示出重要作用。在本研究中,我们检测了从PECAM-1基因敲除小鼠制备的多瘤病毒中T抗原转化的小鼠bEND细胞在培养中增殖以及在小鼠体内形成血管瘤的能力。我们发现这些细胞表达多种内皮细胞标志物,并且与PECAM-1基因野生型bEND细胞具有相似的形态。PECAM-1基因敲除的bEND细胞在基质胶中形成管样结构的能力有限,但注入裸鼠后能迅速形成血管瘤,这与PECAM-1基因野生型bEND细胞非常相似。然而,与PECAM-1基因野生型bEND细胞相比,这些细胞增殖增加、迁移减慢、内皮细胞黏附分子表达改变且黏附性降低。因此,PECAM-1表达缺失影响多瘤病毒中T抗原转化的内皮细胞的增殖、黏附及迁移特性,但不影响它们在小鼠体内迅速形成血管瘤或在基质胶中形成类似毛细血管样结构的能力。