Role of 'Cancer Stem Cells' and Cell Survival in TumorDevelopment and Maintenance

摘要

One critical issue for cancer biology is the nature of the cells that drive the inexorable growth of malignant tumors. Reportsthat only rare cell populations within human leukemias seeded leukemia in mice stimulated the now widely embraced hypoth-esis that only such "cancer stem cells" maintain all tumor growth. However, the mouse microenvironment might instead failto support the dominant human tumor cell populations. Indeed, on syngeneic transplantation of mouse lymphomas andleukemias, we and other investigators have found that a substantial proportion (>10%) of their cells drive tumor growth. Thus,dominant clones rather than rare cancer stem cells appear to sustain many tumors. Another issue is the role of cell survival intumorigenesis. Because tumor development can be promoted by the overexpression of prosurvival genes such as bcl-2, we areexploring the role of endogenous Bcl-2-like proteins in lymphomagenesis. The absence of endogenous Bcl-2 in mice express-ing an Eμ-myc transgene reduced mature B-cell numbers and enhanced their apoptosis, but unexpectedly, lymphoma devel-opment was undiminished or even delayed. This suggests that these tumors originate in an earlier cell type, such as the pro-Bor pre-B cell, and that the nascent neoplastic clones do not require Bcl-2 but may instead be protected by a Bcl-2 relative.