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EPR oximetry of cetuximab-treated head-and-neck tumours in a mouse model
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Norrköping/Finspång. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0001-6148-1053
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. The Skandion Clinic, Uppsala, Sweden.ORCID iD: 0000-0001-8171-2541
Linköping University, Department of Physics, Chemistry and Biology, Chemical Physics. Linköping University, Faculty of Science & Engineering.
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2017 (English)In: Cell Biochemistry and Biophysics, ISSN 1085-9195, E-ISSN 1559-0283, Vol. 75, no 3-4, 299-309 p.Article in journal (Refereed) Published
Abstract [en]

Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a potential connection between the partial oxygen pressure of the tumours and the expression of proteins involved in tumour growth, metabolism and hypoxia.

Place, publisher, year, edition, pages
Humana Press, 2017. Vol. 75, no 3-4, 299-309 p.
Keyword [en]
EPR oximetry, Tumour oxygen pressure, Head and neck cancer, Cetuximab, Hypoxia, Metabolism
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-139472DOI: 10.1007/s12013-017-0814-5ISI: 000415718200006PubMedID: 28756482Scopus ID: 2-s2.0-85026455890OAI: oai:DiVA.org:liu-139472DiVA: diva2:1128829
Note

Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

Available from: 2017-07-29 Created: 2017-07-29 Last updated: 2017-12-12Bibliographically approved

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Gustafsson, HåkanKale, AjayDasu, AlexandruLund, AndersRoberg, Karin
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Division of Radiological SciencesFaculty of Medicine and Health SciencesDepartment of Radiology in Norrköping/FinspångCenter for Medical Image Science and Visualization (CMIV)Division of Neuro and Inflammation ScienceDepartment of Otorhinolaryngology in LinköpingDepartment of Radiation PhysicsChemical PhysicsFaculty of Science & EngineeringDivision of Cell Biology
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