ZFIN ID: ZDB-PUB-101027-8
T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation
Feng, H., Stachura, D.L., White, R.M., Gutierrez, A., Zhang, L., Sanda, T., Jette, C.A., Testa, J.R., Neuberg, D.S., Langenau, D.M., Kutok, J.L., Zon, L.I., Traver, D., Fleming, M.D., Kanki, J.P., and Look, A.T.
Date: 2010
Source: Cancer Cell 18(4): 353-366 (Journal)
Registered Authors: Feng, Hui, Gutierrez, Alejandro, Jette, Cicely A., Kanki, John, Langenau, David, Look, A. Thomas, Traver, David, White, Richard M., Zon, Leonard I.
Keywords: none
MeSH Terms: Animals; Animals, Genetically Modified; Autophagy; Blood Vessels/enzymology; Blood Vessels/pathology* (all 27) expand
PubMed: 20951945 Full text @ Cancer Cell
FIGURES   (current status)
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.