CXCR4 Is a Potential Target for Diagnostic PET/CT Imaging in Barrett's Dysplasia and Esophageal Adenocarcinoma
| Autor: | Margret Schottelius, Anja A. Kühl, Wilko Weichert, Timothy C. Wang, Gabriele Multhoff, Hans-Jürgen Wester, Carlos Gerngroß, Natasha Stephens Münch, Jonas Ingermann, Moritz Jesinghaus, Antonia R. Sepulveda, Haibo Liu, Hsin-Yu Fang, Stefan Stangl, Michael Quante, Michael Schauer, Katja Steiger |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Population medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Biopsy medicine Esophagus education education.field_of_study Tumor microenvironment medicine.diagnostic_test business.industry Cancer Esophageal cancer medicine.disease digestive system diseases 030104 developmental biology medicine.anatomical_structure Oncology Dysplasia 030220 oncology & carcinogenesis Cancer research business Carcinogenesis |
| Zdroj: | Clinical Cancer Research. 24:1048-1061 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-17-1756 |
| Popis: | Purpose: Barrett's esophagus represents an early stage in carcinogenesis leading to esophageal adenocarcinoma. Considerable evidence supports a major role for chronic inflammation and diverse chemokine pathways in the development of Barrett's esophagus and esophageal adenocarcinoma. Experimental Design: Here we utilized an IL1β transgenic mouse model of Barrett's esophagus and esophageal adenocarcinoma and human patient imaging to analyze the importance of CXCR4-expressing cells during esophageal carcinogenesis. Results: IL1β overexpression induces chronic esophageal inflammation and recapitulates the progression to Barrett's esophagus and esophageal adenocarcinoma. CXCR4 expression is increased in both epithelial and immune cells during disease progression in pL2-IL1β mice and also elevated in esophageal adenocarcinoma patient biopsy samples. Specific recruitment of CXCR4-positive (CXCR4+) immune cells correlated with dysplasia progression, suggesting that this immune population may be a key contributor to esophageal carcinogenesis. Similarly, with progression to dysplasia, there were increased numbers of CXCR4+ columnar epithelial cells at the squamocolumnar junction (SCJ). These findings were supported by stronger CXCR4-related signal intensity in ex vivo fluorescence imaging and autoradiography with advanced dysplasia. Pilot CXCR4-directed PET/CT imaging studies in patients with esophageal cancer demonstrate the potential utility of CXCR4 imaging for the diagnosis and staging of esophageal cancer. Conclusion: In conclusion, the recruitment of CXCR4+ immune cells and expansion of CXCR4+ epithelial cells in esophageal dysplasia and cancer highlight the potential of CXCR4 as a biomarker and molecular target for diagnostic imaging of the tumor microenvironment in esophageal adenocarcinoma. Clin Cancer Res; 24(5); 1048–61. ©2017 AACR. |
| Databáze: | OpenAIRE |
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