Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy.

摘要: The phenotypic and functional differences between cells that initiate human breast tumors (cancer stem cells) those comprise the tumor bulk are difficult to study using only primary tissue. We embarked on this hypothesizing cancer cell lines would contain analogous hierarchical differentiation programs found in tumors. Eight (human mammary epithelial cells, MCF10A, MCF7, SUM149, SUM159, SUM1315 MDA.MB.231 were analyzed flow cytometry for CD44, CD24, epithelial-specific antigen (ESA) expression. Limiting dilution orthotopic injections used evaluate initiation, while serial colony-forming unit, reconstitution tumorsphere assays performed assess self-renewal differentiation. Pulse-chase bromodeoxyuridine (5-bromo-2-deoxyuridine [BrdU]) labeling was examine cycle label-retention of cells. Cells treated with paclitaxol 5-fluorouracil test selective resistance chemotherapy, gene expression profile after chemotherapy examined. percentage CD44+/CD24- within does not correlate tumorigenicity, but as few 100 can form when sorted CD44+/CD24-/low/ESA+. Furthermore, CD44+/CD24-/ESA+ self-renew, reconstitute parental line, retain BrdU label, preferentially survive chemotherapy. These data validate use models development testing novel therapeutics aimed at eradicating