1. CXCR7 receptors facilitate the progression of colon carcinoma within lung not within liver
- Author
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David Jérémie Birnbaum, Benchetrit M, Goguet-Surmenian E, Heidy Schmid-Antomarchi, Millet Ma, Annie Schmid-Alliana, Emmanuelle Pradelli, Larbret F, Michiels Jf, Guillemot E, Karimdjee-Soilihi B, and Alemanno P
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Colorectal cancer ,Antineoplastic Agents ,Mice, SCID ,Biology ,chemokines/receptors ,Real-Time Polymerase Chain Reaction ,Metastasis ,Mice ,Cell Line, Tumor ,medicine ,Carcinoma ,Animals ,Humans ,metastasis ,Interleukin 8 ,Receptor ,Receptors, CXCR ,Mice, Inbred BALB C ,Lung ,Interleukin-8 ,Liver Neoplasms ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Chemokine CXCL12 ,CXCR7 antagonists ,animal models ,Gene Expression Regulation, Neoplastic ,Vascular endothelial growth factor A ,Disease Models, Animal ,medicine.anatomical_structure ,Oncology ,colon cancer ,Colonic Neoplasms ,Cancer research ,Disease Progression ,Female ,Translational Therapeutics - Abstract
Background: Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Chemokine-receptor pairs have a critical role in determining the metastatic progression of tumours. Our hypothesis was that disruption of CXCR7/CXCR7 ligands axis could lead to a decrease in CRC metastases. Methods: Primary tumours and metastatic tissues from patients with CRC were tested for the expression of CXCR7 and its ligands. Relevance of CXCR7/CXCR7 ligands for CRC metastasis was then investigated in mice using small pharmacological CXCR7 antagonists and CRC cell lines of human and murine origins, which – injected into mice – enable the development of lung and liver metastases. Results: Following injection of CRC cells, mice treated daily with CXCR7 antagonists exhibited a significant reduction in lung metastases. However, CXCR7 antagonists failed to reduce the extent of liver metastasis. Moreover, there were subtle differences in the expression of CXCR7 and its ligands between lung and liver metastases. Conclusion: Our study suggests that the activation of CXCR7 on tumour blood vessels by its ligands may facilitate the progression of CRC within lung but not within liver. Moreover, we provide evidence that targeting the CXCR7 axis may be beneficial to limit metastasis from colon cancer within the lungs.
- Published
- 2012