通过Hsp70-HMGB1 alarmin复合体对瘤细胞重新繁殖的自调节
Dmitry V Sverchinsky1, Bashar A Alhasan1, Marina A Mikeladze1
1Department of Molecular and Cellular Interaction, Institute of Cytology of Russian Academy of Sciences, Tikhoretsky prospect, 4, St. Petersburg, 194064, Russia.
死亡的瘤细胞释放热冲击蛋白70 (Hsp70) 和高流动性组B1 (HMGB1) 复合体,促进癌症复发. 针对这种Hsp70-HMGB1复合体可能提供新的癌症复发治疗方法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 癌症复发受死亡瘤细胞组件的影响.
- 与损伤相关的分子模式 (DAMPs),如热冲击蛋白70 (Hsp70),涉及到治疗后瘤细胞信号传递.
研究的目的:
- 调查Hsp70在瘤细胞再生和癌症复发中的作用.
- 为了确定参与癌症复发的hsp70结合蛋白.
主要方法:
- 从死亡的瘤细胞和瘤重组模型中利用条件化介质 (CM).
- 采用了亲和性染色学,免疫沉,质谱学,MTT测定和xCELLigence技术.
- 评估细胞增殖标志物,前列腺素E和蛋白质与蛋白质相互作用.
主要成果:
- 从垂死的瘤细胞中得到的条件介质含有引发瘤再生的因素.
- 从CM中去除Hsp70显著降低了瘤重组活动.
- 确定了从垂死的瘤细胞中释放的Hsp70和高流动性组B1 (HMGB1) 复合体,该复合体增强了增殖和复发标志物.
- 抑制Hsp70-HMGB1复合体抑制了瘤生长在体外和体内.
结论:
- 细胞外基质中的Hsp70-HMGB1复合体可能表明癌症复发.
- 准Hsp70-HMGB1复合体为容易复发的癌症提供了潜在的治疗策略.
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