Isolation and molecular characterization of cancer stem cells in MMTVWnt-1 murine breast tumors

In human breast cancers, a phenotypically distinct minority population of tumorigenic cancer (TG) cells (sometimes referred to as cancer stem cells) drives tumor growth when transplanted into immunodeficient mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to studying human breast cancer. To do so, we utilized breast tumors of the MMTVWnt-1 mice. MMTV-Wnt-1 breast tumors were harvested, dissociated into single cell suspensions, and FACS sorted on Thy1, CD24, and CD45. FACS sorted cells were then injected into recipient background FBV/NJ female mice. Thy1+CD24+ cancer cells, which constitute approximately 1-4% of tumor cells were highly enriched for cells capable of regenerating new tumors when compared to cells of the tumor that did not fit this profile (Not Thy1+CD24+). Resultant tumors were of the same phenotypic diversity as the original tumor and behaved in a similar manner when passaged. Microarray analysis comparing Thy1+CD24+ tumor cells to Not Thy1+CD24+ cells identified a list of differentially expressed genes. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells.

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Cho RW, Wang X, Diehn M, Shedden K, Chen GY, Sherlock G, Gurney A, Lewicki J, Clarke MF