**2. Breast cancer stem cells**

The existence of cancer stem cells was first demonstrated in solid tumors by Al Hajj et al., where CSCs were identified from human breast cancer tissue using CD44+ / CD24- Lin as cellular markers (Al-Hajj *et al.*, 2003). They isolated the cells from primary breast cancer or metastatic pleural effusions and injected them directly in to mice or after cellular sorting with the above mentioned markers. They found that CD44+, CD24 were able to form tumors while CD44- , CD24- were unable to form tumors in immunocompromised mice. Further they performed repopulation assays where they found that the tumorigenic population (CD44+ / CD24- Lin-) was able to give rise to phenotypic heterogeneity of the initial tumor. This suggested that the breast cancer stem cells undergo self-renewal and differentiation as in the case of normal stem cells. After this report a large number of studies identified CSC from various other malignancies (Curley *et al.*, 2009; Fang *et al.*, 2005; Kondo *et al.*, 2004; Liu *et al.*, 2007; Prince *et al.*, 2007; Singh *et al.*, 2004).

The normal stem cells reside in a distinct environment called the "stem cell niche". This stem cell niche consists of complex composition of ECM, soluble factors, stromal cells, immune cells which are responsible for maintaining the self renewal ability of stem cells. Similarly the CSCs also depend on similar environment, which may be altered in many ways. Moreover in some of the tumors, the tumor niche has been shown to have a protective role from genotoxic insults (Garcia-Barros *et al.*, 2003). Although much research has been done on understanding the cancer stem cells, very few studies have been carried out on understanding the microenvironment of breast cancer stem cells and their targeting. We believe that understanding the breast cancer microenvironment will offer easily tractable solutions to cancer therapy.
