The role of canonical Wnt signaling in mammary stem cells

Abstract

The mammary gland undergoes extensive growth and involution during postnatal mammary gland development. Tissue expansion and remodeling of the mammary gland suggests the presence of adult stem cells. Transplantation studies validated the existence of mammary stem cells that are able to reconstitute a functional mammary gland. Mammary stem cells are located in the basal cell lineage of the epithelial ducts, but the exact population is not identified yet. However, the Lin- CD29hi CD24+ cell population is reported as stem cell-enriched cell population. Canonical Wnt signaling is shown to be important in adult stem cell populations of different organs. Recent studies also suggest a role for canonical Wnt signaling in mammary stem cells. The first indication came from the MMTV-Wnt1 mouse model, where Wnt signaling increases stem/progenitor cell activity. Another study showed that depletion of Lrp5, the essential co-receptor of Wnt signaling, affects proliferation in the basal cell lineage in vivo. Using Axin2 as marker for Wnt-responsive cells, it was possible to further enrich the stem cell population within the Lin- CD29hi CD24+ cell population and increased Wnt-responsive cells have a competitive advantage in transplantation assays. Together these data indicate an important role for Wnt signaling in mammary stem cells. Recently, the hierarchy of stem cells and progenitor cells was studied using a genetic lineage tracing approach. These experiments showed the existence of two distinct progenitor cell populations for basal and luminal cell lineages instead of a stem cell population. Both progenitor cell populations are Wnt-responsive. Interestingly, under regenerative circumstance a single basal progenitor cell was able to reconstitute a functional mammary gland consisting of both luminal and basal cell lineages. Different studies showed the importance of Wnt signaling in mammary stem or progenitor cells, but further studies are required to assign the exact role of canonical Wnt signaling in the mammary stem cells.