Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models
Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models
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DOI：
10.1016/j.ijrobp.2013.11.008
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发表时间：
2014-03-01
影响因子：
7
通讯作者：
Multhoff, Gabriele
中科院分区：
文献类型：
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作者：
Bayer, Christine;Liebhardt, Michael E.;Multhoff, Gabriele
目的：与正常细胞不同，肿瘤细胞经常在胞浆中过表达热休克蛋白70(Hsp70)，并将其呈现在细胞表面，并主动释放。因此，可溶性热休克蛋白70(SHsp70)可作为一种潜在的肿瘤生物标志物用于监测放射治疗的疗效。方法与材料：检测携带膜型热休克蛋白70(MHsp70)阳性的人头颈部鳞状细胞癌和自发性胰腺导管腺癌(PDAC)小鼠的血浆。对一组荷FaDu肿瘤(0.32 cm(3))的小鼠进行30Gy射线照射，照射后24小时、肿瘤缩小至初始体积的50%、完全缓解后采集血浆。结果：荷瘤小鼠血液中sHsp70水平明显高于对照组。在肿瘤体积为0.01 cm(3)~0.66 cm(3)的范围内，血浆sHsp70水平的升高与肿瘤体积呈正相关。肿瘤的放射诱导消退与sHsp70水平显著降低有关，在完全缓解后，sHsp70水平恢复到对照动物的水平。结论：我们建议将sHsp70作为一种新的生物标志物，用于检测肿瘤和监测癌症患者放射治疗的临床结果。(C)2014年爱思唯尔公司。
Purpose: Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy.Methods and Materials: Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm(3)) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk to 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay.Results: sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm(3) to 0.66 cm(3) was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission.Conclusion: We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients. (C) 2014 Elsevier Inc.