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.