Isolation and characterisation of mouse mammary stem and progenitor cells

点击翻译按钮获取中文摘要

We have discovered the rare adult stem cell from which all breast epithelial tissue is formed. A single stem cell was found to be capable of giving rise to various cell types in the breast, including the secretory units that produce milk and the ductal cells that transmit milk to the nipple. These cell types are responsible for the majority of human breast tumours. However, the precise 'cell of origin' from which cancers ultimately develop is not known. We recently also found that the stem cell population is expanded in at least one model of mammary tumours, suggesting that some tumours may arise from the breast stem cell itself. Using mouse models and cellular assays, our aim is to characterise, for the first time, the hierarchy of stem, progenitor ('daughter cells') and mature cells in the mammary gland. These studies will provide insight into the various cell types that give rise to different types of breast cancer. An important evolving concept in cancer biology is that a rare population of cells resident within a tumour, termed 'cancer stem cells', have indefinite growth potential and drive tumour growth. These cells could even account for resistance to conventional anti-cancer treatment, as cells with stem cell-like properties would be able to proliferate extensively and form new tumours. We will apply our knowledge of normal mammary stem cells to determine whether cancer stem cells are indeed present in mouse tumours. Those findings will have direct relevance to human breast cancer. Utlimately, we wish to identify specific cell surface proteins on stem and precursor cells that could provide therapeutic targets. Our studies will provide new insights into the cell types from which breast cancer arise, and how their fate and tumour-forming capacity can be modified by altering gene expression. Delineation of cancer-prone cells and cancer stem cells could reveal new markers and provide new therapeutic strategies to target breast cancer.