Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma
Aminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS w...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523318303760 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Torsten Kessler Ariane Baumeier Caroline Brand Michael Grau Linus Angenendt Saliha Harrach Ursula Stalmann Lars Henning Schmidt Georg Gosheger Jendrik Hardes Dimosthenis Andreou Johannes Dreischalück Georg Lenz Eva Wardelmann Rolf M. Mesters Christian Schwöppe Wolfgang E. Berdel Wolfgang Hartmann Christoph Schliemann |
| spellingShingle |
Torsten Kessler Ariane Baumeier Caroline Brand Michael Grau Linus Angenendt Saliha Harrach Ursula Stalmann Lars Henning Schmidt Georg Gosheger Jendrik Hardes Dimosthenis Andreou Johannes Dreischalück Georg Lenz Eva Wardelmann Rolf M. Mesters Christian Schwöppe Wolfgang E. Berdel Wolfgang Hartmann Christoph Schliemann Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma Translational Oncology |
| author_facet |
Torsten Kessler Ariane Baumeier Caroline Brand Michael Grau Linus Angenendt Saliha Harrach Ursula Stalmann Lars Henning Schmidt Georg Gosheger Jendrik Hardes Dimosthenis Andreou Johannes Dreischalück Georg Lenz Eva Wardelmann Rolf M. Mesters Christian Schwöppe Wolfgang E. Berdel Wolfgang Hartmann Christoph Schliemann |
| author_sort |
Torsten Kessler |
| title |
Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma |
| title_short |
Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma |
| title_full |
Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma |
| title_fullStr |
Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma |
| title_full_unstemmed |
Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma |
| title_sort |
aminopeptidase n (cd13): expression, prognostic impact, and use as therapeutic target for tissue factor induced tumor vascular infarction in soft tissue sarcoma |
| publisher |
Elsevier |
| series |
Translational Oncology |
| issn |
1936-5233 |
| publishDate |
2018-12-01 |
| description |
Aminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS who were treated by wide resection and uniform chemo-radio-chemotherapy. Using a semiquantitative score with four intensity levels, CD13 was expressed by tumor vasculature, or tumor cells, or both (composite value, intensity scores 1-3) in 93.9% of the STS. In 49.5% tumor cells, in 48.5% vascular/perivascular cells, and in 58.8%, composite value showed strong intensity score 3 staining. Leiomyosarcoma and synovial sarcoma showed low expression; fibrosarcoma and undifferentiated pleomorphic sarcoma showed high expression. We found a significant prognostic impact of CD13, as high expression in tumor cells or vascular/perivascular cells correlated with better relapse-free survival and overall survival. CD13 retained prognostic significance in multivariable analyses. Systemic tTF-NGR resulted in significant growth reduction of CD13-positive human HT1080 sarcoma cell line xenografts. Our results recommend further investigation of tTF-NGR in STS patients. CD13 might be a suitable predictive biomarker for patient selection. |
| url |
http://www.sciencedirect.com/science/article/pii/S1936523318303760 |
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doaj-f259fe8a6c094f9f9602de8024967f502020-11-24T21:30:03ZengElsevierTranslational Oncology1936-52332018-12-0111612711282Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue SarcomaTorsten Kessler0Ariane Baumeier1Caroline Brand2Michael Grau3Linus Angenendt4Saliha Harrach5Ursula Stalmann6Lars Henning Schmidt7Georg Gosheger8Jendrik Hardes9Dimosthenis Andreou10Johannes Dreischalück11Georg Lenz12Eva Wardelmann13Rolf M. Mesters14Christian Schwöppe15Wolfgang E. Berdel16Wolfgang Hartmann17Christoph Schliemann18Department of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, Germany; Address all correspondence to: Torsten Kessler or Wolfgang E. Berdel, Department of Medicine A (Hematology and Oncology), University Hospital Muenster, Albert Schweitzer Campus 1, D-48149 Muenster, Germany.Department of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Orthopedics and Tumor-Orthopedics, University Hospital Muenster, GermanyDepartment of Orthopedics and Tumor-Orthopedics, University Hospital Muenster, GermanyDepartment of Orthopedics and Tumor-Orthopedics, University Hospital Muenster, GermanyDepartment of Orthopedics and Trauma Surgery, Sankt Elisabeth Hospital Guetersloh, GueterslohDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, Germany; Translational Oncology, University Hospital Muenster, Muenster, Germany; Cluster of Excellence EXC 1003, Cells in Motion, Muenster, GermanyGerhard-Domagk-Institute of Pathology, University of Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, Germany; Cluster of Excellence EXC 1003, Cells in Motion, Muenster, Germany; Address all correspondence to: Torsten Kessler or Wolfgang E. Berdel, Department of Medicine A (Hematology and Oncology), University Hospital Muenster, Albert Schweitzer Campus 1, D-48149 Muenster, Germany.Gerhard-Domagk-Institute of Pathology, University of Muenster, Muenster, GermanyDepartment of Medicine A, Hematology, Oncology, University Hospital Muenster, Muenster, GermanyAminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS who were treated by wide resection and uniform chemo-radio-chemotherapy. Using a semiquantitative score with four intensity levels, CD13 was expressed by tumor vasculature, or tumor cells, or both (composite value, intensity scores 1-3) in 93.9% of the STS. In 49.5% tumor cells, in 48.5% vascular/perivascular cells, and in 58.8%, composite value showed strong intensity score 3 staining. Leiomyosarcoma and synovial sarcoma showed low expression; fibrosarcoma and undifferentiated pleomorphic sarcoma showed high expression. We found a significant prognostic impact of CD13, as high expression in tumor cells or vascular/perivascular cells correlated with better relapse-free survival and overall survival. CD13 retained prognostic significance in multivariable analyses. Systemic tTF-NGR resulted in significant growth reduction of CD13-positive human HT1080 sarcoma cell line xenografts. Our results recommend further investigation of tTF-NGR in STS patients. CD13 might be a suitable predictive biomarker for patient selection.http://www.sciencedirect.com/science/article/pii/S1936523318303760 |