T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation.
The molecular 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.
Pubmed ID: 20951945 RIS Download
Animals | Animals, Genetically Modified | Autophagy | Blood Vessels | Cell Aggregation | Cell Line, Tumor | Cell Movement | Disease Progression | Enzyme Activation | Gene Expression Regulation, Leukemic | Humans | Immunohistochemistry | Intercellular Adhesion Molecule-1 | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | Proto-Oncogene Proteins c-akt | Proto-Oncogene Proteins c-bcl-2 | Proto-Oncogene Proteins c-myc | Receptors, Lysosphingolipid | Zebrafish