TY - JOUR
T1 - Validation of heat shock protein 70 as a tumor-specific biomarker for monitoring the outcome of radiation therapy in tumor mouse models
AU - Bayer, Christine
AU - Liebhardt, Michael E.
AU - Schmid, Thomas E.
AU - Trajkovic-Arsic, Marija
AU - Hube, Kathrin
AU - Specht, Hanno M.
AU - Schilling, Daniela
AU - Gehrmann, Mathias
AU - Stangl, Stefan
AU - Siveke, Jens T.
AU - Wilkens, Jan J.
AU - Multhoff, Gabriele
N1 - Funding Information:
This work was funded by the DFG cluster of excellence Munich-Centre for Advanced Photonics ; the German Federal Ministry of Education and Research (BMBF, 0313909 ); the m4-Cluster of Excellence: Personalized Medicine (BMBF, 16EX1021C ); the SFB824 (DFG); the BMBF Kompetenzverbund Strahlenforschung (03NUK007E); and the Klinikum rechts der Isar , Technische Universität München (KKF:15-06).
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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 cm3) 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 cm3 to 0.66 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.
AB - 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 cm3) 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 cm3 to 0.66 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.
UR - http://www.scopus.com/inward/record.url?scp=84893862822&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2013.11.008
DO - 10.1016/j.ijrobp.2013.11.008
M3 - Article
C2 - 24521683
AN - SCOPUS:84893862822
SN - 0360-3016
VL - 88
SP - 694
EP - 700
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -