Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer.
Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer.
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DOI：
10.1186/s13046-015-0166-1
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发表时间：
2015-05-20
期刊：
影响因子：
--
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Zhang Z;Wang M;Zhou L;Feng X;Cheng J;Yu Y;Gong Y;Zhu Y;Li C;Tian L;Huang Q
放射后死亡的肿瘤细胞可促进活肿瘤细胞的增殖，从而导致肿瘤复发和治疗失败。我们前期的研究表明，照射后激活的caspase-3可能参与了肿瘤的再增殖。在这项研究中，我们研究了高迁移率族蛋白1（HMGB 1）是否也参与肿瘤再增殖。照射结肠直肠肿瘤细胞。Westernblot检测照射后肿瘤细胞中裂解的caspase-3（CC 3）和照射后肿瘤细胞培养上清中HMGB 1的表达。然后将大量经照射的结肠直肠肿瘤细胞（饲养细胞）与少量经谷胱甘肽转移酶标记的活结肠直肠肿瘤细胞（报告细胞）共培养，并通过生物发光成像测量报告细胞的增殖。采用免疫组化法检测结直肠癌及癌旁组织中CC 3和HMGB 1蛋白的表达，并分析其与预后的关系。照射后的大肠癌细胞发生凋亡和坏死，并在肿瘤细胞中产生CC 3，在培养细胞的上清液中产生HMGB 1。体外照射后分泌型HMGB 1的表达增加与CC 3水平和增殖细胞核抗原（PCNA）相关。照射的垂死细胞显著刺激活肿瘤细胞增殖。免疫组化结果显示，HMGB 1、CC 3和Ki 67在大肠癌组织中的阳性表达明显高于癌旁组织（p <0.01）。Kaplan-Meier生存分析显示高HMGB 1、CC 3和Ki 67水平与不良预后显著相关（p <0.05，p <0.01）。采用考克斯比例风险模型进行多因素分析，结果显示TNM分期和HMGB 1是影响结直肠癌患者预后的独立因素（p <0.01，p <0.001）。凋亡和坏死细胞均可刺激活肿瘤细胞增殖，肿瘤细胞中CC 3和HMGB 1的表达增加可能是结直肠癌患者预后不良的新标志。本文的在线版本（doi：10.1186/s13046-015-0166-1）包含补充材料，可供授权用户使用。
Dying tumor cells after irradiation could promote the proliferation of living tumor cells might cause tumor relapse and treatment failure. Our previous study showed that activated caspase-3 after irradiation probably participates in tumor repopulation. In this study, we investigated whether high mobility group box 1(HMGB1) is also involved in tumor repopulation. Colorectal tumor cells were irradiated. The cleaved caspase-3 (CC3) in irradiated tumor cells and HMGB1 in the supernatant of irradiated tumor cells were detected by Western blot. A large number of irradiated colorectal tumor cells (feeder cells) were then co-cultured with a small number of luciferase-labeled living colorectal tumor cells (reporter cells) and proliferation of reporter cells was measured by bioluminescence imaging. The CC3 and HMGB1 protein expression in colorectal tumor and peritumoral tissues were detected by immunohistochemistry and their correlation with prognosis were analyzed. The irradiated colorectal tumor cells underwent apoptosis and necrosis and produced CC3 in tumor cells and HMGB1 in the supernatant of cultured cells. The increased expression of secretory HMGB1 correlated with CC3 level and proliferating cell nuclear antigen (PCNA) after irradiation in vitro. The irradiated dying cells remarkably stimulated living tumor cell proliferation. Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01). The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01). Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001). Both apoptotic and necrotic cells could stimulate proliferation of living tumor cells, and the increased expression of CC3 and HMGB1 in tumor cells could be new markers for poor prognosis in colorectal cancer patients. The online version of this article (doi:10.1186/s13046-015-0166-1) contains supplementary material, which is available to authorized users.
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影响因子：
8
作者：
Challa, Sreerupa;Chan, Francis Ka-Ming
通讯作者：
Chan, Francis Ka-Ming
影响因子：
1.6
作者：
Locsey, Katrina L.;Grigorescu, Micaela;Cox, Malcolm E.
通讯作者：
Cox, Malcolm E.
DOI：
10.1007/s00432-011-1067-0
发表时间：
2012-01-01
影响因子：
3.6
作者：
Lin, Liguo;Zhong, Kaihua;Ding, Guodong
通讯作者：
Ding, Guodong
DOI：
10.1158/1078-0432.ccr-13-0495
发表时间：
2013-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kang R;Zhang Q;Zeh HJ 3rd;Lotze MT;Tang D
通讯作者：
Tang D
Caspase 3 介导的癌症放射治疗过程中肿瘤细胞增殖的刺激。
影响因子：
82.9
作者：
通讯作者：
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