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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: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: Denisa L Dragu; Laura G Necula; Coralia Bleotu; Carmen C Diaconu; Mihaela Chivu-Economescu Journal: World J Stem Cells Date: 2015-10-26 Impact factor: 5.326
Authors: Abbas K Samadi; Alan Bilsland; Alexandros G Georgakilas; Amedeo Amedei; Amr Amin; Anupam Bishayee; Asfar S Azmi; Bal L Lokeshwar; Brendan Grue; Carolina Panis; Chandra S Boosani; Deepak Poudyal; Diana M Stafforini; Dipita Bhakta; Elena Niccolai; Gunjan Guha; H P Vasantha Rupasinghe; Hiromasa Fujii; Kanya Honoki; Kapil Mehta; Katia Aquilano; Leroy Lowe; Lorne J Hofseth; Luigi Ricciardiello; Maria Rosa Ciriolo; Neetu Singh; Richard L Whelan; Rupesh Chaturvedi; S Salman Ashraf; H M C Shantha Kumara; Somaira Nowsheen; Sulma I Mohammed; W Nicol Keith; William G Helferich; Xujuan Yang Journal: Semin Cancer Biol Date: 2015-05-05 Impact factor: 15.707
Authors: Michael Tachezy; Hilke Zander; Florian Gebauer; Katharina von Loga; Klaus Pantel; Jakob R Izbicki; Maximilian Bockhorn Journal: J Transl Med Date: 2013-09-30 Impact factor: 5.531