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Published in: Radiation Oncology 1/2014

Open Access 01-12-2014 | Research

Hsp70 - a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck

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

Published in: Radiation Oncology | Issue 1/2014

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Abstract

Background

Tumor but not normal cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface (mHsp70) from where it can be actively released. Therefore, membrane (mHsp70) and soluble Hsp70 (sHsp70) were investigated as potential tumor biomarkers and for monitoring the outcome of radiation therapy.

Methods

Biopsies and blood were collected from patients with squamous cell carcinoma of the head and neck (SCCHN) at different time points (before, during therapy and in the follow-up period). Hsp70 membrane expression was determined on single cell suspensions of tumor biopsies and reference tissues by flow cytometry, sHsp70 protein and antibody levels were determined in the serum of patients and healthy donors by ELISA and NK cell markers that are related to the presence of sHsp70 were analyzed in the patient’s peripheral blood lymphocytes (PBL).

Results

Tumor biopsies exhibited significantly increased mHsp70 expression levels compared to the reference tissue. Soluble Hsp70 levels were significantly higher in SCCHN patients compared to healthy human volunteers and high mHsp70 expression levels on tumor cells were associated with high sHsp70 levels in the serum of patients. Following surgery and radiotherapy sHsp70 levels in patients dropped in patients without tumor relapse in the follow-up period. In contrast to sHsp70 protein, anti-Hsp70 antibody levels remained nearly unaltered in the serum of SCCHN patients before and after therapy. Furthermore, sHsp70 protein but not anti-Hsp70 antibody levels were found to be associated with the tumor volume in SCCHN patients before start of therapy. The expression densities of the activatory NK cell markers CD56, CD94, NKG2D, NKp30, Nkp44, and NKp46 differed in patients following therapeutic intervention. A significant increase in the density of NKG2D was observed in SCCHN patients in the follow-up period after surgery and radiotherapy.

Conclusion

We suggest sHsp70 as a potential biomarker for detecting tumors and for monitoring the clinical outcome of radiotherapy in SCCHN patients.
Appendix
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Metadata
Title
Hsp70 - a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck
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
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2014
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-9-131

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