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  • [Clin Cancer Res.] CXCR4 Is a Potential Target for Diagnostic PET/CT Imaging in Barrett's Dysplasia and Esophageal Adenocarcinoma.

    Technische Universitat Munchen / Michael Quante*

  • 출처
    Clin Cancer Res.
  • 등재일
    2018 Mar 1
  • 저널이슈번호
    24(5):1048-1061.
  • 내용

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    Abstract

    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 esophagealadenocarcinoma.

    Experimental Design: Here we utilized an IL1β transgenic mouse model of Barrett's esophagus and esophagealadenocarcinoma and human patient imaging to analyze the importance of CXCR4-expressing cells during esophagealcarcinogenesis.

    Results: IL1β overexpression induces chronic esophageal inflammation and recapitulates the progression to Barrett'sesophagus 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.

     

     

    Author information

    Fang HY1, Münch NS1, Schottelius M2, Ingermann J1, Liu H3, Schauer M1, Stangl S4, Multhoff G4, Steiger K5, Gerngroß C6, Jesinghaus M5, Weichert W5, Kühl AA7, Sepulveda AR8, Wester HJ2, Wang TC3, Quante M9.

    1 II. Medizinische Klinik, Technische Universitat München, Munich, Germany.
    2 Pharmazeutische Radiochemie, Technische Universitat München, Munich, Germany.
    3 Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York.
    4 Klinik für RadioOnkologie und Strahlentherapie, Technische Universitat München, Munich, Germany.
    5 Institut für Pathologie, Technische Universitat München, Munich, Germany.
    6 Nuklearmedizinische Klinik und Poliklinik, Technische Universitat München, Munich, Germany.
    7 iPATH.Berlin/Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie/Research Center ImmunoSciences, Charité-Campus Benjamin Franklin, Berlin, Germany.
    8 Division of Gastrointestinal Pathology, Columbia University Medical Center, New York, New York.
    9 II. Medizinische Klinik, Technische Universitat München, Munich, Germany. michael.quante@tum.de.

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