Abstract:
Objective:To isolate breast cancer stem/progenitor cells from human basal-like and luminal A breast cancer and to explore their biological behaviors. Methods: Human breast cancer stem/progenitor cells were enriched in suspension cultures as nonadherent mammospheres. Cell growth curve determination and serial sphere formation assay were used to determine proliferation and self-renewing ability of breast cancer stem cells in vitro. Cell proliferation in vivo was also inves-tigated by transplanting tumors in nude mice. The expression of CD 44and CD24in mammosphere-derived cells was evalu -ated by flow cytometry. Results: Cells from both basal-like and luminal A breast cancer can grow in serum-free conditions as mammosphere cultures. Basal-like tumors had a higher percentage (5.1%±1.08%) of stem cells than luminal A tumors (2.02% ±0.30% ) and yielded mammospheres with a larger diameter which contained more cells. Mammosphere cells de-rived from basal-like tumors extensively proliferated in vitro and in vivo, more so than their luminal A counterparts. Mammo -spheres from both basal-like tumors and luminal A tumors were capable of serial passage. Basal-like tumors showed a pro-gressive decrease in mammosphere forming efficiency, increased tendency to differentiate and a failure to passage beyond 15generations with most cells adhering and undergoing terminal differentiation. While mammospheres derived from lumi -nal A tumors could serially passage over 20generations in vitro, increasing numbers of single cells lost their sphere-form-ing potential. CD 44 +/CD 24-tumor cells were detected in all basal-like tumors, while they were either absent or only a small amount appeared in luminal A breast cancer. Conclusion: Breast cancer stem/progenitor cells of the basal-like and luminal A molecular subtype exhibit different stem cell properties of self-renewal, indefinite proliferation and multi-lineage differentia-tion. It appears they have transformed separately from breast epithelial cells.