• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

细胞外S100A4对人骨肉瘤细胞中干扰素-γ诱导凋亡的致敏作用

Sensitization of interferon-gamma induced apoptosis in human osteosarcoma cells by extracellular S100A4.

作者信息

Pedersen Kjetil Boye, Andersen Kristin, Fodstad Øystein, Maelandsmo Gunhild Mari

机构信息

Department of Tumor Biology, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.

出版信息

BMC Cancer. 2004 Aug 19;4:52. doi: 10.1186/1471-2407-4-52.

DOI:10.1186/1471-2407-4-52
PMID:15318945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC515304/
Abstract

BACKGROUND

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.

METHODS

Cell cultures from two human osteosarcoma cell lines, OHS and its anti-S100A4 ribozyme transfected counterpart II-11b, was treated with IFN-gamma and recombinant S100A4 in order to study the sensitizing effects of extracellular S100A4 on IFN-gamma mediated apoptosis. Induction of apoptosis was demonstrated by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase and Lamin B.

RESULTS

In the present work, we found that the S100A4-expressing human osteosarcoma cell line OHS was more sensitive to IFN-gamma-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-gamma. The S100A4/IFN-gamma-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-kappa B (NF-kappa B).

CONCLUSION

In conclusion, we have shown that S100A4 sensitizes osteosarcoma cells to IFN-gamma-mediated induction of apoptosis. Additionally, extracellular S100A4 activates NF-kappa B, but whether these events are causally related remains unknown.

摘要

背景

S100A4是S100家族中一种具有促进转移特性的小钙结合蛋白。最近研究表明，分泌型S100A4蛋白具有多种功能，包括诱导血管生成、刺激细胞运动和神经突延伸。

方法

用IFN-γ和重组S100A4处理两种人骨肉瘤细胞系（OHS及其转染了抗S100A4核酶的对应细胞II-11b）的细胞培养物，以研究细胞外S100A4对IFN-γ介导的细胞凋亡的致敏作用。通过DNA片段化、聚（ADP-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。

结果

在本研究中，我们发现表达S100A4的人骨肉瘤细胞系OHS比II-11b细胞对IFN-γ介导的细胞凋亡更敏感。在OHS细胞的条件培养基中检测到S100A4蛋白，而在II-11b细胞的条件培养基中未检测到，并且向细胞培养基中添加重组S100A4可使II-11b细胞对IFN-γ诱导的细胞凋亡敏感。结果表明，S100A4/IFN-γ介导的细胞凋亡诱导与半胱天冬酶激活无关，但依赖于活性氧的形成。此外，已证明添加细胞外S100A4可激活核因子-κB（NF-κB）。

结论

总之，我们已证明S100A4使骨肉瘤细胞对IFN-γ介导的细胞凋亡诱导敏感。此外，细胞外S100A4激活NF-κB，但这些事件是否存在因果关系尚不清楚。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/534039eaad1b/1471-2407-4-52-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/85bf7228fdd3/1471-2407-4-52-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/0e62e992892e/1471-2407-4-52-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/824467702bf1/1471-2407-4-52-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/8d50927df470/1471-2407-4-52-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/998ad5034138/1471-2407-4-52-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/299b9a8d817e/1471-2407-4-52-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/c8279a72f870/1471-2407-4-52-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/534039eaad1b/1471-2407-4-52-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/85bf7228fdd3/1471-2407-4-52-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/0e62e992892e/1471-2407-4-52-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/824467702bf1/1471-2407-4-52-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/8d50927df470/1471-2407-4-52-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/998ad5034138/1471-2407-4-52-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/299b9a8d817e/1471-2407-4-52-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/c8279a72f870/1471-2407-4-52-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8f/515304/534039eaad1b/1471-2407-4-52-8.jpg

相似文献

1
Sensitization of interferon-gamma induced apoptosis in human osteosarcoma cells by extracellular S100A4.细胞外S100A4对人骨肉瘤细胞中干扰素-γ诱导凋亡的致敏作用
BMC Cancer. 2004 Aug 19;4:52. doi: 10.1186/1471-2407-4-52.
2
Osteopontin--an important downstream effector of S100A4-mediated invasion and metastasis.骨桥蛋白——S100A4 介导的侵袭和转移的重要下游效应物。
Int J Cancer. 2011 Aug 15;129(4):780-90. doi: 10.1002/ijc.25735. Epub 2011 Mar 11.
3
Interferon-gamma-induced suppression of S100A4 transcription is mediated by the class II transactivator.γ干扰素诱导的S100A4转录抑制由II类反式激活因子介导。
Tumour Biol. 2007;28(1):27-35. doi: 10.1159/000097700. Epub 2006 Dec 12.
4
S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme.S100A4参与转移：用抗S100A4核酶转染的骨肉瘤细胞中基质金属蛋白酶及其组织抑制剂的失调
Cancer Res. 1999 Sep 15;59(18):4702-8.
5
RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-kB-dependent MMP-2 and bcl-2 pathway.RNA 干扰抑制 A100A4 通过 NF-κB 依赖性 MMP-2 和 bcl-2 通路减少人肾癌细胞的生长和转移表型。
Eur Rev Med Pharmacol Sci. 2013 Jun;17(12):1669-80.
6
Interferon-gamma suppresses S100A4 transcription independently of apoptosis or cell cycle arrest.干扰素-γ独立于细胞凋亡或细胞周期停滞抑制S100A4转录。
Br J Cancer. 2003 Jun 16;88(12):1995-2001. doi: 10.1038/sj.bjc.6600998.
7
Colchicine induces membrane-associated activation of matrix metalloproteinase-2 in osteosarcoma cells in an S100A4-independent manner.
Biochem Pharmacol. 2003 Dec 15;66(12):2341-53. doi: 10.1016/j.bcp.2003.08.014.
8
Suppression of metastasis-associated S100A4 gene expression by gamma-interferon in human colon adenocarcinoma cells.γ-干扰素对人结肠腺癌细胞中转移相关S100A4基因表达的抑制作用
Br J Cancer. 1999 Apr;80(1-2):127-32. doi: 10.1038/sj.bjc.6690331.
9
Interferon-gamma sensitizes osteosarcoma cells to Fas-induced apoptosis by up-regulating Fas receptors and caspase-8.干扰素-γ通过上调Fas受体和半胱天冬酶-8使骨肉瘤细胞对Fas诱导的凋亡敏感。
Pediatr Blood Cancer. 2004 Dec;43(7):729-36. doi: 10.1002/pbc.20151.
10
The E-F hand calcium-binding protein S100A4 regulates the proliferation, survival and differentiation potential of human osteosarcoma cells.E-F手型钙结合蛋白S100A4调节人骨肉瘤细胞的增殖、存活和分化潜能。
Cell Physiol Biochem. 2013;32(4):1083-96. doi: 10.1159/000354508. Epub 2013 Nov 4.

引用本文的文献

1
Constructing a ferroptosis-related prognostic model for osteosarcoma based on scRNA-seq dataset and WGCNA analysis.基于单细胞RNA测序数据集和加权基因共表达网络分析构建骨肉瘤铁死亡相关预后模型。
Int J Clin Exp Pathol. 2025 Jul 15;18(7):335-350. doi: 10.62347/QVON7675. eCollection 2025.
2
S100A4 contributes to colorectal carcinoma aggressive behavior and to chemoradiotherapy resistance in locally advanced rectal carcinoma.S100A4促进结直肠癌的侵袭性行为，并导致局部晚期直肠癌对放化疗产生耐药性。
Sci Rep. 2024 Dec 28;14(1):31338. doi: 10.1038/s41598-024-82814-9.
3
Protective effect of cilostazol and verapamil against thioacetamide-induced hepatotoxicity in rats may involve Nrf2/GSK-3β/NF-κB signaling pathway.

本文引用的文献

1
Downregulation of the antiapoptotic MCL-1 protein and apoptosis in MA-11 breast cancer cells induced by an anti-epidermal growth factor receptor-Pseudomonas exotoxin a immunotoxin.抗表皮生长因子受体-绿脓杆菌外毒素a免疫毒素诱导MA-11乳腺癌细胞中抗凋亡蛋白MCL-1下调及细胞凋亡
Int J Cancer. 2004 Nov 10;112(3):475-83. doi: 10.1002/ijc.20371.
2
Immunofluorometric assay for the metastasis-related protein S100A4: release of S100A4 from normal blood cells prohibits the use of S100A4 as a tumor marker in plasma and serum.
Tumour Biol. 2004 Jan-Apr;25(1-2):31-40. doi: 10.1159/000077721.
3
Nuclear localization of the metastasis-related protein S100A4 correlates with tumour stage in colorectal cancer.转移相关蛋白S100A4的核定位与结直肠癌的肿瘤分期相关。
西洛他唑和维拉帕米对硫代乙酰胺诱导的大鼠肝毒性的保护作用可能涉及Nrf2/GSK-3β/NF-κB信号通路。
Toxicol Res (Camb). 2022 Aug 9;11(5):718-729. doi: 10.1093/toxres/tfac045. eCollection 2022 Oct.
4
Interferon gamma induces protective non-canonical signaling pathways in primary neurons.γ干扰素在原代神经元中诱导保护性非经典信号通路。
J Neurochem. 2015 Oct;135(2):309-22. doi: 10.1111/jnc.13250. Epub 2015 Aug 31.
5
S100 protein family in human cancer.人类癌症中的 S100 蛋白家族。
Am J Cancer Res. 2014 Mar 1;4(2):89-115. eCollection 2014.
6
S100 proteins as diagnostic and prognostic markers in colorectal and hepatocellular carcinoma.S100蛋白作为结直肠癌和肝细胞癌的诊断及预后标志物
Hepat Mon. 2012 Oct;12(10 HCC):e7240. doi: 10.5812/hepatmon.7240. Epub 2012 Oct 12.
7
S100A4 in esophageal cancer: is this the one to blame?S100A4 在食管癌中的作用：这是罪魁祸首吗？
World J Gastroenterol. 2012 Aug 14;18(30):3931-5. doi: 10.3748/wjg.v18.i30.3931.
8
S100A4 expression in xenograft tumors of human carcinoma cell lines is induced by the tumor microenvironment.人癌细胞系异种移植瘤中 S100A4 的表达受肿瘤微环境诱导。
Am J Pathol. 2011 May;178(5):2389-96. doi: 10.1016/j.ajpath.2011.01.022.
9
The metastasis-promoting protein S100A4 regulates mammary branching morphogenesis.促转移蛋白 S100A4 调控乳腺分支形态发生。
Dev Biol. 2011 Apr 15;352(2):181-90. doi: 10.1016/j.ydbio.2010.12.033. Epub 2010 Dec 31.
10
Overexpression of S100A4 in human cancer cell lines resistant to methotrexate.人肿瘤细胞株耐甲氨蝶呤过程中 S100A4 的过度表达。
BMC Cancer. 2010 Jun 1;10:250. doi: 10.1186/1471-2407-10-250.
J Pathol. 2003 Aug;200(5):589-95. doi: 10.1002/path.1381.
4
S100B inhibits myogenic differentiation and myotube formation in a RAGE-independent manner.S100B以不依赖晚期糖基化终末产物受体（RAGE）的方式抑制肌源性分化和肌管形成。
Mol Cell Biol. 2003 Jul;23(14):4870-81. doi: 10.1128/MCB.23.14.4870-4881.2003.
5
Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity.钙卫蛋白（S100A8/S100A9），一种来自中性粒细胞的具有广泛凋亡诱导活性的炎症蛋白复合物。
Biol Pharm Bull. 2003 Jun;26(6):753-60. doi: 10.1248/bpb.26.753.
6
Interferon-gamma suppresses S100A4 transcription independently of apoptosis or cell cycle arrest.干扰素-γ独立于细胞凋亡或细胞周期停滞抑制S100A4转录。
Br J Cancer. 2003 Jun 16;88(12):1995-2001. doi: 10.1038/sj.bjc.6600998.
7
Mitochondrial membrane permeabilization and superoxide production during apoptosis. A single-cell analysis.细胞凋亡过程中的线粒体膜通透性改变与超氧化物生成。单细胞分析
J Biol Chem. 2003 Apr 11;278(15):12645-9. doi: 10.1074/jbc.M210826200. Epub 2003 Jan 30.
8
Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton.
Biochim Biophys Acta. 2002 Nov 4;1600(1-2):74-83. doi: 10.1016/s1570-9639(02)00447-8.
9
Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death?凋亡诱导因子（AIF）：细胞死亡中保守的非半胱天冬酶依赖性途径的关键？
J Cell Sci. 2002 Dec 15;115(Pt 24):4727-34. doi: 10.1242/jcs.00210.
10
Interferon-gamma augments CD95(APO-1/Fas) and pro-caspase-8 expression and sensitizes human vascular endothelial cells to CD95-mediated apoptosis.γ干扰素增强CD95（APO-1/Fas）和前半胱天冬酶-8的表达，并使人血管内皮细胞对CD95介导的凋亡敏感。
Am J Pathol. 2002 Oct;161(4):1485-95. doi: 10.1016/s0002-9440(10)64424-0.