Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Int J Radiat Oncol Biol Phys. 2014 Mar 1;88(3):694-700. doi: 10.1016/j.ijrobp.2013.11.008.
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.
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.
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.
We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.
与正常细胞相比，肿瘤细胞常常在细胞质中过度表达热休克蛋白 70（Hsp70），将其呈现在细胞表面，并积极释放。因此，可溶性 Hsp70（sHsp70）被作为一种潜在的肿瘤生物标志物，用于监测放射治疗的效果。
研究了携带膜 Hsp70（mHsp70）阳性的 FaDu 头颈部鳞状细胞癌和自发性胰腺导管腺癌（PDAC）的荷瘤小鼠的血浆。对一组 FaDu 肿瘤（0.32cm³）小鼠进行 30Gy 照射，在肿瘤缩小至起始体积的 50%以及完全消退后，分别在照射后 24 小时、肿瘤缩小过程中收集血浆。采用酶联免疫吸附试验定量检测血浆中的 sHsp70 水平。
荷瘤小鼠的血浆 sHsp70 水平明显高于对照组。观察到在 0.01cm³至 0.66cm³范围内，sHsp70 血浆水平与肿瘤体积的增加呈正相关。肿瘤的放射消退与 sHsp70 水平的显著降低相关，在完全消退后，sHsp70 水平恢复至对照组水平。
我们提出 sHsp70 作为一种创新性的肿瘤标志物，用于检测肿瘤，并监测癌症患者放射治疗的临床效果。
