Sensitization of interferon-gamma induced apoptosis in human osteosarcoma cells by extracellular S100A4.
Sensitization of interferon-gamma induced apoptosis in human osteosarcoma cells by extracellular S100A4.
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DOI：
10.1186/1471-2407-4-52
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发表时间：
2004-08-19
期刊：
影响因子：
3.8
通讯作者：
Maelandsmo GM
中科院分区：
文献类型：
--
作者：
Pedersen KB;Andersen K;Fodstad Ø;Maelandsmo GM
S100 A4是S100家族的一种小的钙结合蛋白，具有促进转移的特性。近年来，分泌型S100 A4蛋白被证实具有多种功能，包括诱导血管生成、刺激细胞运动和神经突起延伸。用IFN-γ和重组S100 A4处理人骨肉瘤细胞株OHS和转染抗S100 A4核酶的II-11b细胞，研究细胞外S100 A4对IFN-γ介导的细胞凋亡的增敏作用。通过DNA片段化、多聚腺苷二磷酸核糖聚合酶和核纤层蛋白B的裂解来证明细胞凋亡的诱导。在本研究中，我们发现表达S100 A4的人骨肉瘤细胞系OHS对IFN-γ介导的凋亡比II-11b细胞更敏感。在OHS细胞的条件培养基中检测到S100 A4蛋白，但在II-11b细胞中未检测到，并且向细胞培养基中添加重组S100 A4使II-11b细胞对IFN-γ诱导的凋亡敏感。S100 A4/IFN-γ介导的细胞凋亡的诱导不依赖于caspase的激活，但依赖于活性氧的形成。此外，细胞外S100 A4的添加被证明激活核因子-κB（NF-κB）。总之，我们已经证明，S100 A4敏感的骨肉瘤细胞IFN-γ介导的诱导凋亡。此外，细胞外S100 A4激活NF-κB，但这些事件是否有因果关系仍不清楚。
S100A4 is a small Ca2+-binding protein of the S100 family with metastasis-promoting properties. Recently, secreted S100A4 protein has been shown to possess a number of functions, including induction of angiogenesis, stimulation of cell motility and neurite extension. Cell cultures from two human osteosarcoma cell lines, OHS and its anti-S100A4 ribozyme transfected counterpart II-11b, was treated with IFN-γ and recombinant S100A4 in order to study the sensitizing effects of extracellular S100A4 on IFN-γ mediated apoptosis. Induction of apoptosis was demonstrated by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase and Lamin B. In the present work, we found that the S100A4-expressing human osteosarcoma cell line OHS was more sensitive to IFN-γ-mediated apoptosis than the II-11b cells. S100A4 protein was detected in conditioned medium from OHS cells, but not from II-11b cells, and addition of recombinant S100A4 to the cell medium sensitized II-11b cells to apoptosis induced by IFN-γ. The S100A4/IFN-γ-mediated induction of apoptosis was shown to be independent of caspase activation, but dependent on the formation of reactive oxygen species. Furthermore, addition of extracellular S100A4 was demonstrated to activate nuclear factor-κB (NF-κB). In conclusion, we have shown that S100A4 sensitizes osteosarcoma cells to IFN-γ-mediated induction of apoptosis. Additionally, extracellular S100A4 activates NF-κB, but whether these events are causally related remains unknown.
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影响因子：
20.3
作者：
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DOI：
10.1016/s1570-9639(02)00447-8
发表时间：
2002-11-04
影响因子：
3.2
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通讯作者：
Decaestecker, C