Christine Bayer1, Michael E Liebhardt1, Thomas E Schmid1, Marija Trajkovic-Arsic2, Kathrin Hube1, Hanno M Specht1, Daniela Schilling3, Mathias Gehrmann1, Stefan Stangl1, Jens T Siveke2, Jan J Wilkens1, Gabriele Multhoff4. 1. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 2. II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 3. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich, Germany. 4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich, Germany. Electronic address: Gabriele.multhoff@lrz.tum.de.
Abstract
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.
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 humansquamous 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 cancerpatients.
Authors: Mathias K Gehrmann; Melanie A Kimm; Stefan Stangl; Thomas E Schmid; Peter B Noël; Ernst J Rummeny; Gabriele Multhoff Journal: Int J Nanomedicine Date: 2015-09-08
Authors: Naoya Murakami; Annett Kühnel; Thomas E Schmid; Katarina Ilicic; Stefan Stangl; Isabella S Braun; Mathias Gehrmann; Michael Molls; Jun Itami; Gabriele Multhoff Journal: Radiat Oncol Date: 2015-07-22 Impact factor: 3.481
Authors: Mathias Gehrmann; Melchiorre Cervello; Giuseppe Montalto; Francesco Cappello; Alessandro Gulino; Clemens Knape; Hanno M Specht; Gabriele Multhoff Journal: Front Immunol Date: 2014-07-01 Impact factor: 7.561
Authors: Mathias Gehrmann; Hanno M Specht; Christine Bayer; Markus Brandstetter; Barbara Chizzali; Marciana Duma; Stephanie Breuninger; Kathrin Hube; Sophie Lehnerer; Valerie van Phi; Eva Sage; Thomas E Schmid; Michael Sedelmayr; Daniela Schilling; Wolfgang Sievert; Stefan Stangl; Gabriele Multhoff Journal: Radiat Oncol Date: 2014-06-09 Impact factor: 3.481