High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy
High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy
复制标题
DOI：
10.1016/j.ejca.2012.09.016
复制
发表时间：
2013-02-01
影响因子：
8.4
通讯作者：
Kuniyasu, Hiroki
中科院分区：
文献类型：
--
作者：
Luo, Yi;Chihara, Yoshitomo;Kuniyasu, Hiroki
检测高迁移率族蛋白1(HMGB1)在化疗诱导的细胞死亡中的作用。用曲古抑菌素A(TSA)或阿霉素(DXR)处理CT26小鼠结肠癌细胞。DXR可增加CT26细胞培养液中HMGB1的浓度，而TSA则不能。在CT26双侧皮下肿瘤模型中，在单个肿瘤内注射DXR或TSA。注射后，DXR组小鼠血清HMGB1浓度是TSA组的10倍。在DXR治疗后，对侧和残留肿瘤显示出比TSA治疗更显著的生长。在小鼠模型中，DXR可促进肺和肝转移，但TSA不能。经抗HMGB1抗体治疗后，DXR增强的转移被阻断。在癌症休眠模型中，DXR诱导静止的CT26细胞再生。HMGB1通过Toll样受体(TLR)4诱导U937单核细胞分泌肿瘤坏死因子-α，但HMGB1通过晚期糖基化终产物受体(RAGE)抑制U937细胞的免疫激活。RAGE对CT26细胞核因子kappaB活化的影响比TLR4更明显。这些发现表明，用坏死诱导剂处理的坏死癌细胞释放的HMGB1通过RAGE激活促进残留癌细胞的再生和转移。(C)2012爱思唯尔有限公司。保留所有权利。
The role of the high mobility group box 1 (HMGB1) protein in chemotherapy-induced cell death was examined. CT26 mouse colon cancer cells were treated with trichostatin A (TSA; apoptosis inducer) or doxorubicin (DXR; necrosis inducer). DXR increased HMGB1 concentration in CT26 cell culture medium, whereas TSA did not. In a CT26 bilateral subcutaneous tumour model, DXR or TSA was injected in a single tumour. After injection, serum HMGB1 concentration in DXR-treated mice was 10 times higher than that in TSA-treated mice. After DXR treatment, the contralateral and remnant tumours showed more pronounced growth than did those treated with TSA. In mouse models, lung and liver metastasis was enhanced by DXR but not by TSA. DXR-enhanced metastasis was abrogated by anti-HMGB1 antibody treatment. In a cancer dormancy model, DXR induced regrowth of quiescent CT26 cells. HMGB1 induced tumour necrosis factor-a secretion via Toll-like receptor (TLR) 4 in U937 monocytes; however, HMGB1 decreased the number of U937 cells, resulting in restriction of immune activation via receptor for advanced glycation endproducts (RAGE). RAGE showed a more pronounced effect on nuclear factor kappa B activation than did TLR4 in CT26 cells. These findings suggest that HMGB1 released from necrotic cancer cells treated with a necrosis inducer enhances regrowth and metastasis of remnant cancer cells via RAGE activation. (C) 2012 Elsevier Ltd. All rights reserved.