Targeting breast cancer stem cells
Abstract
The cancer stem cell (CSC) hypothesis suggests that self-renewing CSC population can maintain tumour and also able to differentiate into non-self-renewing cell populations. The CSC hypothesis assumes that the most common targets of transformation are tissue-resident stem or progenitor cells. Clinically, chemo- and radiation-therapy are ineffectively to target CSCs because CSCs are predicted to mediate tumour recurrence after therapy. Present, it is quite challenge to develop CSC-specific therapeutics based on levels of cell-surface proteins, molecular pathways, cell cycle quiescence, and microRNA signalling. Unbiased high-throughput siRNA or small molecule screening and the development of agents targeting known stem cell regulatory pathways are approaches to targeting CSCs. Now, we review possibility of both approaches in targeting breast CSC (Sean et al., 2010).
1. What is a cancer stem cell?
Cancer stem cells is defined based on three functional characteristics of the cells, which are the ability to initiate tumours in immunocompromised or syngeneic mice, the capacity to differentiate into the non-self-renewing cells and self-renewal capacity measured by tumour formation in secondary mice (Clarke et al., 2006).
2. Hierarchal organization of the human breast
Human breast contains a lot of ducts. The ducts is composed of luminal epithelial and myoepithelial cells. Luminal lineage is make up of ductal and alveolar cells. During pregnancy, luminal lineage lines the ducts, while myoepithelial cells act as basal, contractile cells works as forcing secreting milk proteins. During puberty and multiple pregnancies, cells with extensive proliferative and regenerative properties associated with stem cells in growth of breast epithelium.
Some studies suggested the presence of long-lived cells, such as women will increase risk of developing breast cancer later in life if she exposes to radiation as teenagers (Land and...