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EPR Oximetry of Cetuximab-Treated Head-and-Neck Tumours in a Mouse Model
Linkoping Univ, Dept Radiol Norrkoping, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci IMH, Linkoping, Sweden.;Linkoping Univ, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden..
Linkoping Univ, Dept Clin & Expt Med, Div Otorhinolaryngol & Head & Neck Surg, Linkoping, Sweden..
Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Skandion Clin, Uppsala, Sweden..
Linkoping Univ, Dept Phys Chem & Biol IFM, Uppsala, Sweden..
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2017 (English)In: Cell Biochemistry and Biophysics, ISSN 1085-9195, E-ISSN 1559-0283, Vol. 75, no 3-4, p. 299-309Article 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 (R)) 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-1 alpha 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-1 alpha 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 INC , 2017. Vol. 75, no 3-4, p. 299-309
Keywords [en]
EPR oximetry, Tumour oxygen pressure, Head and neck cancer, Cetuximab, Hypoxia, Metabolism
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-342658DOI: 10.1007/s12013-017-0814-5ISI: 000415718200006PubMedID: 28756482OAI: oai:DiVA.org:uu-342658DiVA, id: diva2:1186284
Conference
10th EPR Workshop on Applications of EPR in Biology and Medicine, 2016, Krakow, POLAND
Funder
Swedish Research CouncilAvailable from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-02-28Bibliographically approved

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