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A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer

¹ McGowan Institute for Regenerative Medicine, Department of Pathology, ² Center for Biologic Imaging, Department of Cell Biology and Physiology, and ³ UPMC Liver Cancer Center, Starzl Transplant Institute, Department of Surgery, University of Pittsburgh Medical School; ⁴ Department of Human Genetics, University of Pittsburgh Graduate School of Public Health and Cytogenetics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Requests for reprints: Eric Lagasse, McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical School, 100 Technology Drive, Suite 200, Pittsburgh PA, 15219-3130. Phone: 412-235-5147; Fax: 412-235-5110; E-mail: Lagasse{at}Pitt.edu.

Key Words: Chromosomal Instability in Cancer Stem Cells

Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability. [Cancer Res 2008;68(17):6932–41]

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