Title of article :
T-Lymphoblastic Lymphoma Cells Express High Levels of BCL2, S1P1, and ICAM1, Leading to a Blockade of Tumor Cell Intravasation
Author/Authors :
Feng، نويسنده , , Hui and Stachura، نويسنده , , David L. and White، نويسنده , , Richard M. and Gutierrez، نويسنده , , Alejandro and Zhang، نويسنده , , Lu and Sanda، نويسنده , , Takaomi and Jette، نويسنده , , Cicely A. and Testa، نويسنده , , Joseph R. and Neuberg، نويسنده , , Donna S. and Langenau، نويسنده , , David M. and Kutok، نويسنده , , Jeffery L. and Zon، نويسنده , , Leonard I. and Traver، نويسنده , , David and Fleming، نويسنده , , Mark D. and Kanki، نويسنده , , John P. and Look، نويسنده , , A. Thomas، نويسنده ,
Abstract :
Summary
lecular events underlying the progression of T-lymphoblastic lymphoma (T-LBL) to acute T-lymphoblastic leukemia (T-ALL) remain elusive. In our zebrafish model, concomitant overexpression of bcl-2 with Myc accelerated T-LBL onset while inhibiting progression to T-ALL. The T-LBL cells failed to invade the vasculature and showed evidence of increased homotypic cell-cell adhesion and autophagy. Further analysis using clinical biopsy specimens revealed autophagy and increased levels of BCL2, S1P1, and ICAM1 in human T-LBL compared with T-ALL. Inhibition of S1P1 signaling in T-LBL cells led to decreased homotypic adhesion in vitro and increased tumor cell intravasation in vivo. Thus, blockade of intravasation and hematologic dissemination in T-LBL is due to elevated S1P1 signaling, increased expression of ICAM1, and augmented homotypic cell-cell adhesion.
