The CXCR4/CXCR7/CXCL12 Axis Is Involved in a Secondary but Complex Control of Neuroblastoma Metastatic Cell Homing
| Autor: | Katia Balmas Bourloud, Marjorie Flahaut, Pu Yan, Julie Liberman, Jean-Marc Joseph, Annick Mühlethaler-Mottet, Kelly Ascencao, Nicolas Jauquier, Nicole Gross |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Chemokine
Receptors CXCR4 lcsh:Medicine Biology CXCR4 Mice Neuroblastoma Bone Marrow Adrenal Glands medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis Receptor lcsh:Science Lung Cell Proliferation Receptors CXCR Multidisciplinary Cell growth lcsh:R medicine.disease Neuroblastic Tumor Chemokine CXCL12 Gene Expression Regulation Neoplastic Liver biology.protein Cancer research lcsh:Q Signal transduction Homing (hematopoietic) Research Article Signal Transduction |
| Zdroj: | PloS one PLoS ONE PLoS ONE, Vol 10, Iss 5, p e0125616 (2015) Plos One, vol. 10, no. 5, pp. e0125616 |
| Popis: | Neuroblastoma (NB) is one of the most deadly solid tumors of the young child, for which new efficient and targeted therapies are strongly needed. The CXCR4/CXCR7/CXCL12 chemokine axis has been involved in the progression and organ-specific dissemination of various cancers. In NB, CXCR4 expression was shown to be associated to highly aggressive undifferentiated tumors, while CXCR7 expression was detected in more differentiated and mature neuroblastic tumors. As investigated in vivo, using an orthotopic model of tumor cell implantation of chemokine receptor-overexpressing NB cells (IGR-NB8), the CXCR4/CXCR7/CXCL12 axis was shown to regulate NB primary and secondary growth, although without any apparent influence on organ selective metastasis. In the present study, we addressed the selective role of CXCR4 and CXCR7 receptors in the homing phase of metastatic dissemination using an intravenous model of tumor cell implantation. Tail vein injection into NOD-scid-gamma mice of transduced IGR-NB8 cells overexpressing CXCR4, CXCR7, or both receptors revealed that all transduced cell variants preferentially invaded the adrenal gland and typical NB metastatic target organs, such as the liver and the bone marrow. However, CXCR4 expression favored NB cell dissemination to the liver and the lungs, while CXCR7 was able to strongly promote NB cell homing to the adrenal gland and the liver. Finally, coexpression of CXCR4 and CXCR7 receptors significantly and selectively increased NB dissemination toward the bone marrow. In conclusion, CXCR4 and CXCR7 receptors may be involved in a complex and organ-dependent control of NB growth and selective homing, making these receptors and their inhibitors potential new therapeutic targets. |
| Databáze: | OpenAIRE |
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