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Is Tumor Growth Sustained by Rare Cancer Stem Cells or Dominant Clones?

The Walter and Eliza Hall Institute of Medical Research Melbourne, Victoria, Australia

Requests for reprints: Jerry Adams and Andreas Strasser, Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria, 3050 Australia. Phone: 61393452491; Fax: 61393470852; E-mail: adams{at}wehi.edu.au and strasser{at}wehi.edu.au.

Key Words: therapeutic targets • tumor heterogeneity • tumor propagation

A key issue for cancer biology and therapy is whether the relentless growth of a tumor is driven by a substantial proportion of its cells or exclusively by a rare subpopulation, commonly termed "cancer stem cells." Support for the cancer stem cell model has been stimulated by experiments in which human tumor cells were transplanted into immunodeficient mice. Most notably, in human acute myeloid leukemia, only a minute proportion of the cells, displaying a defined phenotype, could seed leukemia in mice. Xenotransplantation, however, may fail to reveal many tumor growth–sustaining cells because the foreign microenvironment precludes essential interactions with support cells. In studies that instead have transplanted mouse leukemias and lymphomas into syngeneic animals, most of the tumors seem to be maintained by the dominant cell population, and only a few types of mouse leukemia seem to be sustained by a minor tumor growth–sustaining subpopulation. The collective evidence suggests that various tumors may span the spectrum between the extremes represented by the two models. If tumor growth can indeed be sustained either by rare cancer stem cells or dominant clones or both, as current evidence suggests, curative therapy for many types of tumors will most likely require targeting all the tumor cell populations. [Cancer Res 2008;68(11):4018–21]

This article has been cited by other articles:

				J.M Adams, P.N. Kelly, A. Dakic, S. Carotta, S.L. Nutt, and A. Strasser Role of "Cancer Stem Cells" and Cell Survival in Tumor Development and Maintenance Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.004v1. [Abstract] [PDF]