title: Validation of heat shock protein 70 as a tumor-specific biomarker for monitoring the outcome of radiation therapy in tumor mouse models.
abstract: OBJECTIVE
  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
  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.
  
  
  CONCLUSIONS
  We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Christine
authors: C
authors: Bayer
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Michael E
authors: ME
authors: Liebhardt
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Thomas E
authors: TE
authors: Schmid
authors: II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Marija
authors: M
authors: Trajkovic-Arsic
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Kathrin
authors: K
authors: Hube
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Hanno M
authors: HM
authors: Specht
authors: 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.
authors: Daniela
authors: D
authors: Schilling
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Mathias
authors: M
authors: Gehrmann
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Stefan
authors: S
authors: Stangl
authors: II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Jens T
authors: JT
authors: Siveke
authors: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Jan J
authors: JJ
authors: Wilkens
authors: 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.
authors: Gabriele
authors: G
authors: Multhoff
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood*; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D064593:Heterografts; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy; D011829:Radiation Dosage; D018874:Spheroids, Cellular / Q000378:metabolism / Q000528:radiation effects; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins