CXCR4/SDF-1α-mediated chemotaxis in an in vivo model of metastatic esophageal carcinoma.

BACKGROUND/AIM: The chemokine receptor CXCR4 and its ligand (stromal cell-derived factor-1alpha; SDF-1α) play an important role in tumor cell chemotaxis and metastatic homing of esophageal carcinoma. Several methods are available to examine tumor cell migration in vitro. However, in vivo chemotaxis is subject to complex tumor-host interactions. The aim of this study was to establish an in vivo model of chemotaxis for esophageal carcinoma that allows the examination of tumor cell migration and metastatic homing in the complex microenvironment.

MATERIALS AND METHODS

CXCR4 expression of OE19 adenocarcinoma cells was determined by immunostaining in an orthotopic esophageal model. SDF-1α-mediated migration of cells was examined in vitro. An in vivo model of chemotaxis and metastasis was established by subcutaneous injection of OE19 cells into NMRI/nu mice and by daily stimulation with SDF-1α.

RESULTS

CXCR4 is expressed in the primary tumor and in the metastatic tissue. CXCR4-positive OE19 cells are susceptible to SDF-1α-mediated migration. The novel in vivo model leads to developement of metastases in liver, lung, peritoneum and retroperitoneum after stimulation with SDF-1α but not with PBS, and revealed an SDF-1α dose-dependent migratory effect.

CONCLUSION

As metastasis is still the leading cause of tumor-related death, it is essential to investigate the complex tumor-host interactions involved in metastatic homing. We established an in vivo model of chemotaxis and metastasis for esophageal carcinoma, which allows investigation and inhibition of CXCR4/SDF-1α-mediated cell survival and proliferation, chemotaxis and homing, adhesion, and tumor angiogenesis.