The new portrait of mammary gland stem cells

Breast cancer occurs at rate of 1 out of 7. After so many years of research, even though treatment has been dramatically improved and survival rate and length significantly increased, there is still not cure for the disease. The possible existence of mammary gland stem cell and breast cancer stem cell [1, 2] lights the hope for finding a cure to this deadly disease. The rational behind is that once the stem cell can be isolated, the signalling pathways that regulate its proliferation, self-renewal, survival and differentiation will be illustrated, and this might shed light on the mechanisms of breast cancer formation, therefore leading to a better therapeutic treatment. Existence of stem cell in normal mammary gland has been convincingly demonstrated by Kordon and Smith [1]. In their report, an entire mammary gland could be regenerated with the progeny of a single cell following transplantation into cleared mammary fat pads. By definition, mammary gland stem cells are those that rarely divide and persist throughout reproductive life. Classical markers [3] for identifying and purifying mammary stem cells are label retention (tritiated thymidine or BrdU), stem cell antigen Sca-1 expression, ability to exclude dyes such as Hoechst 33342 or rhodamine 123 (side population-SP, e.g. Hoechst 33342 negative) because of elevated expression of membrane transporter proteins, such as P-glycoproteins, and " small light " cell by electronic microscopy. However, these profiling methods are controversial and confusing. Sometimes, for a layman, it is very difficult to handle. But this situation is about to change with two recent publications in Nature. In January, Shackleton et al published " Generation of a functional mammary gland from a single stem cell " [4]. In this report, the authors cleared mammary gland mixture with CD31 (endothelial marker), CD45 and TER119 (haematopoietic antigens) by FACS sorting (Lin-population). Using repopulating cleared mammary fat pad (Mammary repopulating 'units'-MRUs) as criteria, they were able to increase the MRUs from 1/4900 to 1/64 just by applying two more markers on Lin-population-CD29 (beta1-integrin) and CD24 (heat-stable antigen). Lin-CD29 hi Cd24 + cells have expended differentiation ability and colony-formation ability. A single Lin-CD29 hi CD24 + cell can repopulate cleared mammary fat pad and develop into a fully functioning mammary gland, demonstrating its high proliferating and multi-lineage differentiation capacity in vivo. Lin-CD29 hi Cd24 + cells can self-renew. In mammary gland of MMTV-Wnt-1 transgenic mice, Lin-CD29 hi Cd24 + population are increased and mammary gland …