Direct cell adhesion to the angiopoietins mediated by integrins
Direct cell adhesion to the angiopoietins mediated by integrins
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DOI：
10.1074/jbc.m100282200
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发表时间：
2001-07-13
影响因子：
4.8
通讯作者：
Morla, AO
中科院分区：
文献类型：
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作者：
Carlson, TR;Feng, YZ;Morla, AO
血管生成素-1 （ang -1）或其同源受体Tie2的基因消融会破坏小鼠胚胎的血管生成。ang -1基因敲除小鼠生长血管中的内皮细胞呈圆形外观，并且彼此之间及其下层基底膜的相关性较差(Dumont， D. J., Gradwohl， G., Fong， G. H., purl， M. C, Gertsenstein， M., Auerbach, a .和Breitman， M. L. (1994) Genes Dev. 8, 1897-1909；Sate， T. N., Tozawa， Y., Deutsch， U., Wolburg- buchholz， K., Fujiwara， Y., Gendron-Maguire， M., Gridley， T., Wolburg， H., Risau， W.和Qin， Y. (1995) Nature 376, 70-74；Suri， C, Jones， P. F, Patan， S., Bartunkova， S., Maisonpierre， P. C, Davis， S., Sate， T. N., and Yancopoulos， G. D. (1996) Cell 87, 1171-1180)。因此，ang - 1可能调节内皮细胞粘附。在这项研究中，我们询问ang - 1是否可能作为细胞粘附的直接底物。人脐静脉内皮细胞（HUVECs）在不同底物上短时间的粘附和扩散良好。在血管生成素-2 （ang2）包被的表面上也观察到类似的结果，尽管细胞在ang2上没有很好地扩散。ang - 1支持HUVEC迁移，而Ang-2不支持，且与生长因子活性无关。当同样的实验在缺乏或稳定表达Tie2的成纤维细胞中进行时，可以看到与HUVECs相似的结果，这表明血管生成素的粘附与Tie2无关，并不局限于内皮细胞。有趣的是，当整合素阻断剂被包括在这些检测中时，对任何一种血管生成素的粘附都显著降低。此外，缺乏a，整合素亚基的中国仓鼠卵巢b2细胞不粘附ang - 1，但可粘附Ang-8。人类a -整合素亚基在这些细胞中的稳定表达恢复了对ang - 1的粘附，并促进了对Ang-a的粘附增加。我们还发现ang - 1和Ang-8与玻璃体连接蛋白的结合具有选择性。这些结果表明，除了调节Tie2信号外，ang - 1和Ang-2还可以直接支持整合素介导的细胞粘附。
Genetic ablation of angiopoietin-1 (Ang-l) or of its cognate receptor, Tie2, disrupts angiogenesis in mouse embryos. The endothelial cells in growing blood vessels of Ang-l knockout mice have a rounded appearance and are poorly associated with one another and their underlying basement membranes (Dumont, D. J., Gradwohl, G., Fong, G. H., purl, M. C., Gertsenstein, M., Auerbach, A, and Breitman, M. L. (1994) Genes Dev. 8, 1897-1909; Sate, T. N., Tozawa, Y., Deutsch, U., Wolburg-Buchholz, K., Fujiwara, Y., Gendron-Maguire, M., Gridley, T., Wolburg, H., Risau, W., and Qin, Y. (1995) Nature 376, 70-74; Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S., Sate, T. N., and Yancopoulos, G. D. (1996) Cell 87, 1171-1180). It is therefore possible that Ang-l regulates endothelial cell adhesion. In this study we asked whether Ang-l might act as a direct substrate for cell adhesion. Human umbilical vein endothelial cells (HUVECs) plated for a brief period on different substrates were found to adhere and spread well on Ang-l. Similar results were seen on angiopoietin-2 (Ang-2)-coated surfaces, although cells did not spread well on Ang-2. Ang-l, but not Ang-2, supported HUVEC migration, and this was independent of growth factor activity. When the same experiments were done with fibroblasts that either lacked, or stably expressed, Tie2, results similar to those with HUVECs were seen, suggesting that adhesion to the angiopoietins was independent of Tie2 and not limited to endothelial cells. Interestingly, when integrin-blocking agents were included in these assays, adhesion to either angiopoietin was significantly reduced. Moreover, Chinese hamster ovary-B2 cells lacking the a, integrin subunit did not adhere to Ang-l, but they did adhere to Ang-8. Stable expression of the human a, integrin subunit in these cells rescued adhesion to Ang-l and promoted an increase in adhesion to Ang-a, We also found that Ang-l and Ang-8 bind rather selectively to vitronectin. These results suggest that, beyond their role in modulating Tie2 signaling, Ang-l and Ang-2 can directly support cell adhesion mediated by integrins.