Cancer stem cells (CSCs) are able to maintain and regenerate the tumour, so it is critical to eliminate them to prevent cancer relapse. To do this, we must not only be able to identify CSCs, but to understand what drives their stem cell properties. We have recently identified a potential CSC marker in the mouse mammary gland, and are now investigating functional differences underlying stem cell behaviour in the breast cancer model.
Like organs derived from stem cells, tumours are also organised in a cellular hierarchy, with so-called cancer stem cells (CSC) at the apex. The identities of stem and progenitor cell populations in the mammary gland, as well as tumour-initiating cells that give rise to breast cancer, are poorly understood.
We recently identified a rare progenitor cell population in the adult murine mammary gland marked by the surface protein Lgr6 (Blaas et al., 2016). Lineage tracing analysis showed that Lgr6-positive cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. Oncogenic mutations in Lgr6-positive cells resulted in luminal mammary gland tumours. Conversely, depletion of Lgr6-positive cells in the MMTV-PyMT model of mammary tumourigenesis dramatically impaired tumour growth.
This work indicates that Lgr6 marks adult mammary gland progenitor cells that can initiate tumours, and CSCs of breast tumours required for efficient tumour maintenance (Blaas et al., 2016). We want to characterise Lgr6-positive CSCs in mammary tumours, using functional and molecular approaches to find differences between cancer stem cells and non-stem cells, with the ultimate goal of identifying strategies to eliminate tumour stem cells in breast cancer.