A variety of human solid tumors, including breast cancer, are considered to embrace a hierarchical organization in which only infrequent tumor-initiating cancer stem cells are truly responsible for tumor formation rather than the non-tumorigenic majority. However, these cancer stem cells remain elusive and vaguely characterized due to the absence of suitable cultivation systems and lack of specific markers. To study breast cancer stem cells in our model system that mimics Her2-positive subtype of human breast cancer, we cultivated primary tumor cells and grew tumorspheres under non-adherent condition. Cells capable of forming tumorspheres retained ability of self-renewal and capacity for initiating tumors that recapitulate the original heterogeneity, which resembled normal stem cells within normal tissues. We also investigated how the cancer stem cell fate was determined by the extracellular matrix (collagen, fibronectin and laminin), and found that cell differentiation was induced, resulting in attenuated tumorigenic potential
