Document Detail


T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation.
MedLine Citation:
PMID:  20951945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hui Feng; David L Stachura; Richard M White; Alejandro Gutierrez; Lu Zhang; Takaomi Sanda; Cicely A Jette; Joseph R Testa; Donna S Neuberg; David M Langenau; Jeffery L Kutok; Leonard I Zon; David Traver; Mark D Fleming; John P Kanki; A Thomas Look
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer cell     Volume:  18     ISSN:  1878-3686     ISO Abbreviation:  Cancer Cell     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-03     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  353-66     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Autophagy
Blood Vessels / enzymology,  pathology*
Cell Aggregation
Cell Line, Tumor
Cell Movement
Disease Progression
Enzyme Activation
Gene Expression Regulation, Leukemic
Humans
Immunohistochemistry
Intercellular Adhesion Molecule-1 / genetics,  metabolism*
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / enzymology,  genetics,  metabolism*,  pathology*
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
Proto-Oncogene Proteins c-myc / metabolism
Receptors, Lysosphingolipid / antagonists & inhibitors,  genetics,  metabolism*
Zebrafish
Grant Support
ID/Acronym/Agency:
1K01DK074555/DK/NIDDK NIH HHS; 1K08CA133103/CA/NCI NIH HHS; 3K01AR055619-03S1/AR/NIAMS NIH HHS; CA068484/CA/NCI NIH HHS; CA077429/CA/NCI NIH HHS; K01 AR055619/AR/NIAMS NIH HHS; K01AR05562190-01A1/AR/NIAMS NIH HHS; K08 CA133103/CA/NCI NIH HHS; K08 CA133103-01/CA/NCI NIH HHS; K08 CA133103-02/CA/NCI NIH HHS; K08 CA133103-03/CA/NCI NIH HHS; K08 CA133103-04/CA/NCI NIH HHS; K99 CA134743-01A1/CA/NCI NIH HHS; K99CA134743/CA/NCI NIH HHS; L40 CA124083-01/CA/NCI NIH HHS; L40 CA124083-02/CA/NCI NIH HHS; R00 CA134743/CA/NCI NIH HHS; R01 CA077429-13/CA/NCI NIH HHS; T32-HL086344/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/Receptors, Lysosphingolipid; 126547-89-5/Intercellular Adhesion Molecule-1; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections
Comment In:
Cancer Cell. 2010 Oct 19;18(4):297-9   [PMID:  20951938 ]

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