Inhibition of the SDF-1α–CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells from ATL patients and murine lymphoblastoid cells from HTLV-I Tax transgenic mice
| العنوان: | Inhibition of the SDF-1α–CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells from ATL patients and murine lymphoblastoid cells from HTLV-I Tax transgenic mice |
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| المؤلفون: | Tetsutaro Sata, Takashi Kimura, Hidekatsu Iha, Hideki Hasegawa, Takahiro Tsuji, Masao Ogata, Takashi Okamoto, William W. Hall, Yasuko Orba, Akira Kawaguchi, Akira Ainai, Hirofumi Sawa |
| المصدر: | Blood. 114:2961-2968 |
| بيانات النشر: | American Society of Hematology, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, Male, Genetically modified mouse, Benzylamines, Receptors, CXCR4, Pathology, medicine.medical_specialty, Stromal cell, Anti-HIV Agents, Immunoblotting, Immunology, Mice, Transgenic, Mice, SCID, Biology, Cyclams, Biochemistry, CXCR4, Immunoenzyme Techniques, Mice, Cell Movement, Heterocyclic Compounds, medicine, Animals, Humans, Leukemia-Lymphoma, Adult T-Cell, Lymphocytes, RNA, Messenger, Cells, Cultured, Aged, Human T-lymphotropic virus 1, Reverse Transcriptase Polymerase Chain Reaction, Lymphoblast, Cell migration, Gene Products, tax, Cell Biology, Hematology, Middle Aged, medicine.disease, biology.organism_classification, Chemokine CXCL12, Mice, Inbred C57BL, Leukemia, Cell culture, Cancer research, Female |
| الوصف: | Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T lymphotropic virus type I, and presents as an aggressive leukemia with characteristic widespread leukemic cell infiltration into visceral organs and skin. The molecular mechanisms associated with leukemic cell infiltration are poorly understood. We have used mouse models of ATL to investigate the role of chemokines in this process. Transfer of splenic lymphomatous cells from transgenic to SCID mice reproduces a leukemia and lymphoma that is histologically identical to human disease. It could be shown that lymphomatous cells exhibit specific chemotactic activity in response to stromal cell-derived factor-1alpha (SDF-1alpha). Lymphomatous cells exhibited surface expression of CXCR4, the specific receptor of SDF-1alpha. AMD3100, a CXCR4 antagonist, was found to inhibit both SDF-1alpha-induced migration and phosphorylation of extracellular signal-related kinase 1/2. Investigation of cultured cells from human ATL patients revealed identical findings. Using the SCID mouse model, it could be demonstrated that AMD3100 inhibited infiltration of lymphomatous cells into liver and lung tissues in vivo. These results demonstrate the involvement of the SDF-1alpha/CXCR4 interaction as one mechanism of leukemic cell migration and this may provide a novel target as part of combination therapy for ATL. |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1f569eb1383f1ec87f9c517724f7e98Test https://doi.org/10.1182/blood-2008-11-189308Test |
| رقم الانضمام: | edsair.doi.dedup.....a1f569eb1383f1ec87f9c517724f7e98 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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