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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• 作者：Christine Bayer ; Michael E. Liebhardt ; Thomas E. Schmid ; Marija Trajkovic-Arsic ; Kathrin Hube ; Hanno M. Specht ; Daniela Schilling ; Mathias Gehrmann ; Stefan Stangl ; Jens T. Siveke ; Jan J. Wilkens ; Gabriele Multhoff
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：1 March, 2014
• 年：2014
• 卷：88
• 期：3
• 页码：694-700
• 全文大小：1001 K

文摘

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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聽cm³) was irradiated with 30聽Gy, and plasma was collected 24聽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聽cm³ to 0.66聽cm³ 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.