Mammary Stem Cell Susceptibility to Carcinogenesis

Abstract : Mammary tumor formation is thought to be the consequence of transformation of undifferentiated pluripotent stem cells. Little is known about the character of mammary gland stem cells. Examination of mammary gland development has indicated that there may be three distinct types of stem/progenitor cells (S/PC); those which only form ductal structures, those which only form alveolar structures and those which form all mammary gland structures. The goal of this work was to isolate S/PC from rat mammary glands using the recently described techniques of mammosphere formation and Hoechst dye-exclusion. Additionally, we sought to characterize the S/PC populations as to their ability to differentiate in solid matrix and their expression of certain antigens. Lastly, we aimed to determine whether the susceptibility of mammospheres (containing S/PC and transit amplifying cells TAC) to carcinogens varied compared to the intact mammary epithelial organoid (primarily TAC) . We cultured rat mammospheres and demonstrated two hallmarks of S/PC, their ability to self renew and to differentiate in solid matrix. We also isolated side-population (SP) cells which excluded Hoechst dye and reformed mammospheres. Immunostaining results were similar for organoids and mammospheres. Further work is needed to clearly assess which cell type is necessary for carcinogenesis.