Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression.
Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression.
复制标题
DOI：
10.1091/mbc.e04-12-1082
复制
发表时间：
2005-02
影响因子：
3.3
通讯作者：
Karen D. Cowden Dahl;S. E. Robertson;V. Weaver;M. Simon
中科院分区：
文献类型：
--
作者：
Karen D. Cowden Dahl;S. E. Robertson;V. Weaver;M. Simon
缺氧诱导因子（HIF）缺陷胎盘表现出许多缺陷，包括细胞命运的改变，缺乏胎儿血管生成，细胞过少，以及对母体组织的侵袭性差。HIF是由α和β芳烃受体核转运子或ARNT亚基组成的异二聚体转录因子。我们使用未分化的滋养层干细胞（TS）来表征HIF依赖的粘附、迁移和侵袭。与野生型细胞相比，Arnt（-/-）和Hifalpha（-/-）TS细胞表现出向玻连蛋白的粘附和迁移减少。此外，该缺陷与整合素α v β 3的细胞表面表达降低和该整合素在局灶性粘连中的表达显著降低相关。由于粘附和迁移在肿瘤进展中的重要性（除了胎盘发育），我们检查了在1.5%氧气中培养B16 F0黑色素瘤细胞的影响（O（2））。在1.5%O（2）中培养B16 F0黑色素瘤细胞导致α v β 3整合素表面表达增加，并增加了对玻连蛋白的粘附和迁移。总之，这些数据表明HIF和O（2）张力通过增加细胞表面α v β 3整合素的表达影响胎盘侵袭和肿瘤迁移。
Hypoxia-inducible factor (HIF)-deficient placentas exhibit a number of defects, including changes in cell fate adoption, lack of fetal angiogenesis, hypocellularity, and poor invasion into maternal tissue. HIF is a heterodimeric transcription factor consisting of alpha and beta aryl hydrocarbon receptor nuclear translocator or ARNT) subunits. We used undifferentiated trophoblast stem (TS) cells to characterize HIF-dependent adhesion, migration, and invasion. Arnt(-/-) and Hifalpha(-/-) TS cells exhibit reduced adhesion and migration toward vitronectin compared with wild-type cells. Furthermore, this defect is associated with decreased cell surface expression of integrin alphavbeta3 and significantly decreased expression of this integrin in focal adhesions. Because of the importance of adhesion and migration in tumor progression (in addition to placental development), we examined the affect of culturing B16F0 melanoma cells in 1.5% oxygen (O(2)). Culturing B16F0 melanoma cells at 1.5% O(2) resulted in increased alphavbeta3 integrin surface expression and increased adhesion to and migration toward vitronectin. Together, these data suggest that HIF and O(2) tension influence placental invasion and tumor migration by increasing cell surface expression of alphavbeta3 integrin.