Marius Otto1, Sebastian Blatt2, Andreas Pabst3, Robert Mandic4, Johanna Schwarz5, Andreas Neff1, Thomas Ziebart6. 1. Interdisciplinary Head & Neck Oncology Laboratory, Department for Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstrasse, D-35033, Marburg, Germany. 2. Clinic for Oral and Maxillofacial Surgery, University Medical Center Mainz, Mainz, Germany. 3. Clinic for Oral and Maxillofacial Surgery, Federal Armed Forces Hospital Koblenz, Koblenz, Germany. 4. Interdisciplinary Head & Neck Oncology Laboratory, Department of Otolaryngology, Head & Neck Surgery, University Hospital Marburg, Marburg, Germany. 5. Department of Mathematics and Computer Science, Research Group for Bioinformatics, Philipps-Universität Marburg, Marburg, Germany. 6. Interdisciplinary Head & Neck Oncology Laboratory, Department for Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstrasse, D-35033, Marburg, Germany. ziebart@med.uni-marburg.de.
Abstract
OBJECTIVES: The aim of this murine in vivo study was to investigate whether buffy coat-derived putative endothelial progenitor cells (BCEPC) alter tumor growth and neovascularization in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: A murine xenograft model using the PCI-13 oral cancer cell line was deployed of which n = 24 animals received 2 × 106 BCEPC by transfusion whereas the control group (n = 24) received NaCl (0.9%) instead. Tumor size, volume, and capillary density were determined by sonography and measurement with a caliper. Immunohistochemical analysis was carried out with antibodies specific for Cytokeratins, Flt-4, Podoplanin, and Vimentin. RESULTS: In the experimental group, systemic application of BCEPC significantly increased tumor volume to 362.49% (p = 0.0012) and weight to 352.38% (p = 0.0018) as well as vascular densities to 162.15% (p = 0.0021) compared with control tumors. In addition, BCEPC-treated xenografts exhibited higher Cytokeratin expression levels by a factor of 1.47 (p = 0.0417), Podoplanin by a factor of 3.3 (p = 0.0020) and Vimentin by a factor of 2.5 (p = 0.0001), respectively. CONCLUSIONS: Immunohistochemical investigations support the notion that BCEPC transfusion influences neovascularization and lymphatic vessel density, thereby possibly promoting tumor progression. Future studies, which will include gene expression analysis, should help to define the possible role of BCEPC during OSCC progression in more detail. CLINICAL RELEVANCE: Endothelial progenitor cells (EPCs) could serve as a target structure for the treatment of OSCC and possibly other solid tumors.
OBJECTIVES: The aim of this murine in vivo study was to investigate whether buffy coat-derived putative endothelial progenitor cells (BCEPC) alter tumor growth and neovascularization in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: A murine xenograft model using the PCI-13 oral cancer cell line was deployed of which n = 24 animals received 2 × 106 BCEPC by transfusion whereas the control group (n = 24) received NaCl (0.9%) instead. Tumor size, volume, and capillary density were determined by sonography and measurement with a caliper. Immunohistochemical analysis was carried out with antibodies specific for Cytokeratins, Flt-4, Podoplanin, and Vimentin. RESULTS: In the experimental group, systemic application of BCEPC significantly increased tumor volume to 362.49% (p = 0.0012) and weight to 352.38% (p = 0.0018) as well as vascular densities to 162.15% (p = 0.0021) compared with control tumors. In addition, BCEPC-treated xenografts exhibited higher Cytokeratin expression levels by a factor of 1.47 (p = 0.0417), Podoplanin by a factor of 3.3 (p = 0.0020) and Vimentin by a factor of 2.5 (p = 0.0001), respectively. CONCLUSIONS: Immunohistochemical investigations support the notion that BCEPC transfusion influences neovascularization and lymphatic vessel density, thereby possibly promoting tumor progression. Future studies, which will include gene expression analysis, should help to define the possible role of BCEPC during OSCC progression in more detail. CLINICAL RELEVANCE: Endothelial progenitor cells (EPCs) could serve as a target structure for the treatment of OSCC and possibly other solid tumors.
Entities:
Keywords:
Endothelial progenitor cell; Lymphangiogenesis; Neovascularization; Oral cancer
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