Involvement of CXCR4 chemokine receptor in metastastic HER2-positive esophageal cancer.
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Involvement of CXCR4 chemokine receptor in metastastic HER2-positive esophageal cancer. / Gros, Stephanie; Kurschat, Nina; Drenckhan, Astrid; Dohrmann, Thorsten; Forberich, Evelyn; Harms-Effenberger, Katharina; Reichelt, Uta; Hoffman, Robert M; Pantel, Klaus; Kaifi, Jussuf; Izbicki, Jakob R.
in: PLOS ONE, Jahrgang 7, Nr. 10, 10, 2012, S. 47287.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Involvement of CXCR4 chemokine receptor in metastastic HER2-positive esophageal cancer.
AU - Gros, Stephanie
AU - Kurschat, Nina
AU - Drenckhan, Astrid
AU - Dohrmann, Thorsten
AU - Forberich, Evelyn
AU - Harms-Effenberger, Katharina
AU - Reichelt, Uta
AU - Hoffman, Robert M
AU - Pantel, Klaus
AU - Kaifi, Jussuf
AU - Izbicki, Jakob R.
PY - 2012
Y1 - 2012
N2 - A functional linkage of the structurally unrelated receptors HER2 and CXCR4 has been suggested for breast cancer but has not been evaluated for esophageal carcinoma. The inhibition of HER2 leads to a reduction of primary tumor growth and metastases in an orthotopic model of esophageal carcinoma. The chemokine receptor CXCR4 has been implicated in metastatic dissemination of various tumors and correlates with poor survival in esophageal carcinoma. The aim of this study was to investigate a correlation between the expression levels of HER2 and CXCR4 and to evaluate the involvement of CXCR4-expression in HER2-positive esophageal carcinoma. The effects of HER2-inhibition with trastuzumab and of CXCR4-inhibition with AMD3100 on primary tumor growth, metastatic homing, and receptor expression were evaluated in vitro and in an orthotopic model of metastatic esophageal carcinoma using MRI for imaging. The clinical relevance of HER2- and CXCR4-expression was examined in esophageal carcinoma patients. A significant correlation of HER2- and CXCR4-expression in primary tumor and metastases exists in the orthotopic model. Trastuzumab and AMD3100 treatment led to a significant reduction of primary tumor growth, metastases and micrometastases. HER2-expression was significantly elevated under AMD3100 treatment in the primary tumor and particularly in the metastases. The positive correlation between HER2- and CXCR4-expression was validated in esophageal cancer patients. The correlation of CXCR4- and HER2-expression and the elevation of HER2-expression and reduction of metastases through CXCR4-inhibition suggest a possible functional linkage and a role in tumor dissemination in HER2-positive esophageal carcinoma.
AB - A functional linkage of the structurally unrelated receptors HER2 and CXCR4 has been suggested for breast cancer but has not been evaluated for esophageal carcinoma. The inhibition of HER2 leads to a reduction of primary tumor growth and metastases in an orthotopic model of esophageal carcinoma. The chemokine receptor CXCR4 has been implicated in metastatic dissemination of various tumors and correlates with poor survival in esophageal carcinoma. The aim of this study was to investigate a correlation between the expression levels of HER2 and CXCR4 and to evaluate the involvement of CXCR4-expression in HER2-positive esophageal carcinoma. The effects of HER2-inhibition with trastuzumab and of CXCR4-inhibition with AMD3100 on primary tumor growth, metastatic homing, and receptor expression were evaluated in vitro and in an orthotopic model of metastatic esophageal carcinoma using MRI for imaging. The clinical relevance of HER2- and CXCR4-expression was examined in esophageal carcinoma patients. A significant correlation of HER2- and CXCR4-expression in primary tumor and metastases exists in the orthotopic model. Trastuzumab and AMD3100 treatment led to a significant reduction of primary tumor growth, metastases and micrometastases. HER2-expression was significantly elevated under AMD3100 treatment in the primary tumor and particularly in the metastases. The positive correlation between HER2- and CXCR4-expression was validated in esophageal cancer patients. The correlation of CXCR4- and HER2-expression and the elevation of HER2-expression and reduction of metastases through CXCR4-inhibition suggest a possible functional linkage and a role in tumor dissemination in HER2-positive esophageal carcinoma.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Reproducibility of Results
KW - Disease Models, Animal
KW - Mice
KW - Cell Movement
KW - Cell Line, Tumor
KW - Neoplasm Metastasis
KW - Receptors, CXCR4/metabolism
KW - Receptor, erbB-2/metabolism
KW - Antibodies, Monoclonal, Humanized/pharmacology
KW - Body Weight/drug effects
KW - Bone Marrow/pathology
KW - Esophageal Neoplasms/metabolism/pathology
KW - Heterocyclic Compounds/pharmacology
KW - Tumor Burden
KW - Up-Regulation/drug effects
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Reproducibility of Results
KW - Disease Models, Animal
KW - Mice
KW - Cell Movement
KW - Cell Line, Tumor
KW - Neoplasm Metastasis
KW - Receptors, CXCR4/metabolism
KW - Receptor, erbB-2/metabolism
KW - Antibodies, Monoclonal, Humanized/pharmacology
KW - Body Weight/drug effects
KW - Bone Marrow/pathology
KW - Esophageal Neoplasms/metabolism/pathology
KW - Heterocyclic Compounds/pharmacology
KW - Tumor Burden
KW - Up-Regulation/drug effects
U2 - 10.1371/journal.pone.0047287
DO - 10.1371/journal.pone.0047287
M3 - SCORING: Journal article
VL - 7
SP - 47287
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 10
M1 - 10
ER -
