title: Effective inhibition of metastases and primary tumor growth with CTCE-9908 in esophageal cancer.
abstract: BACKGROUND
  In spite of multimodular treatment, the therapeutic options for esophageal carcinoma are limited, and metastases remain the leading cause of tumor-related mortality. Expression of the chemokine receptor CXCR4 significantly correlates with poor survival rates in patients with esophageal carcinoma and is associated with lymph node and bone marrow metastases. The aim of this study was to evaluate the effect of the CXCR4 antagonist CTCE-9908 on metastatic homing and primary tumor growth in vitro and in vivo in an orthotopic xenograft model of esophageal cancer.
  
  
  METHODS
  OE19 cells were examined for stromal cell-derived factor 1 alpha-mediated migration under CTCE-9908 treatment. The CTCE-9908 treatment was further evaluated in an in vitro proliferation assay and orthotopic esophageal model, accompanied by magnetic resonance imaging. Tumor and metastases were immunohistochemically examined for CXCR4 expression.
  
  
  RESULTS
  CTCE-9908 has an inhibitory effect on stromal cell-derived factor 1 alpha-mediated migration and proliferation of OE19 cells. Treatment with CTCE-9908 in the orthotopic esophageal model leads to a reduction of metastatic spread and primary tumor growth. This was confirmed by magnetic resonsance imaging. Treatment with CTCE-9908 results in altered CXCR4 expression pattern exhibiting a high degree of variability.
  
  
  CONCLUSIONS
  CTCE-9908 effectively inhibits OE19 cell migration and proliferation in vitro, reduces metastases to lung, liver, and lymph nodes in vivo, and moreover leads to tumor growth reduction in an orthotopic model of esophageal carcinoma.
authors.affiliation: Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Drenckhan
authors.forename: Nina
authors.initials: N
authors.lastname: Kurschat
authors.forename: Thorsten
authors.initials: T
authors.lastname: Dohrmann
authors.forename: Nina
authors.initials: N
authors.lastname: Raabe
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Koenig
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Gros
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008279:Magnetic Resonance Imaging; D051379:Mice; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D019718:Receptors, CXCR4 / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C540323:CTCE-9908; C527276:CXCR4 protein, human; D010455:Peptides; D019718:Receptors, CXCR4