| Autor: |
Cardona CI; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Rodriguez A; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Torres VC; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Sanchez A; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Torres A; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Vazquez AE; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Wagler AE; Public Health Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA., Brissette MA; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Bill CA; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA., Vines CM; Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79936, USA. |
| Abstrakt: |
C-C Chemokine Receptor 7 (CCR7) mediates T-cell acute lymphoblastic leukemia (T-ALL) invasion of the central nervous system (CNS) mediated by chemotactic migration to C-C chemokine ligand 19 (CCL19). To determine if a CCL19 antagonist, CCL19 8-83 , could inhibit CCR7-induced chemotaxis and signaling via CCL19 but not CCL21, we used transwell migration and Ca 2+ mobilization signaling assays. We found that in response to CCL19, human T-ALL cells employ β2 integrins to invade human brain microvascular endothelial cell monolayers. In vivo, using an inducible mouse model of T-ALL, we found that we were able to increase the survival of the mice treated with CCL19 8-83 when compared to non-treated controls. Overall, our results describe a targetable cell surface receptor, CCR7, which can be inhibited to prevent β2-integrin-mediated T-ALL invasion of the CNS and potentially provides a platform for the pharmacological inhibition of T-ALL cell entry into the CNS. |
