Fishin' for Answers

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Science  12 Nov 2010:
Vol. 330, Issue 6006, pp. 891
DOI: 10.1126/science.330.6006.891-a

Tumors that remain spatially confined are usually treated more effectively than those that disseminate to other parts of the body. Thus there is great interest in identifying the molecular signals that control tumor cell dissemination in order to reveal new therapeutic targets. The related cancers T-lymphoblastic lymphoma (T-LBL) and acute T-lymphoblastic leukemia (T-ALL) are intriguing examples because despite their genetic similarity, T-LBL develops as a localized disease in some patients, whereas in others the disease progresses to T-ALL and spreads rapidly.

To explore the molecular basis for this, Feng et al. studied T-LBL development in zebrafish, a model organism in which genes of interest can be readily manipulated and the effects of these manipulations are easily monitored because the fish are transparent. Spatially confined T-LBL showed activation of intercellular adhesion signaling pathways that prevented invasion of the tumor cells into blood vessels. The genes implicated in this process encoded BCL-2, S1P1, and ICAM1, which interestingly were expressed more highly in clinical samples of T-LBL as compared to T-ALL. Conversely, T-LBL that progressed to T-ALL exhibited activation of the protein kinase AKT. Patients with T-LBL and T-ALL often receive identical treatments; however, this work suggests that patients may benefit from therapies that target the distinct molecular features of their cancers.

Cancer Cell 18, 353 (2010).

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