Stem cells in mammary development and carcinogenesis: implications for prevention and treatment

Recently, substantial progress has been made in the identification and characterization of stem and progenitor cells in the mouse and human mammary gland. Furthermore, there is increasing evidence that a variety of neoplasms, including breast cancer, may result from transformation of normal stem and progenitor cells. Consistent with this model of carcinogenesis, a breast cancer stem cell population, with the phenotype CD24-CD44+ lineage, was recently identified utilizing flow-cytometry based cell sorting and nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenografts. As few as 200 cells of this cancer stem cell population were capable of generating tumors in animals, whereas the bulk of the tumor population was tumorigenic only when implanted in high numbers. Like their normal counterparts, the cancer stem cells have the ability to self-renew, driving tumorigenicity and possibly recurrence and metastasis, and have the ability to differentiate, generating the heterogeneity of the tumors. This stem cell model of carcinogenesis has important implications for understanding the basic biology of breast cancer, as well as other cancers. Furthermore, the concept of cancer as a disease of stem and progenitor cells has profound implications for the development of new strategies for cancer prevention and therapy.