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Cancer Stem Cells: A Possible Path to a Cure

July 5th, 2009

Cancer stem cells (CSCs), as their name implies, are stem cells that have been discovered to reside within cancerous tumors. Tumors are made up of a heterogeneous mixture of cells. Consequently, if the growth comes from a common origin it must be a cell, or cells, capable of becoming many different types of cells. This makes stem cells a very likely suspect as they, by definition, are able to give rise to a variety of cells. CSCs have been broadly defined as cells within a tumor that are able to self-renew, regenerating a population of multipotent CSCs, as well as differentiate into other cells, which can create the heterogeneity seen in tumors (Vermeulen et al., 2008).

Although the theory of cancer stem cells has been around since the 1970s (Hamburger and Salmon, 1977), recently it has gained a spotlight in the scientific community. The first functional identification of CSCs was in 1997 in acute myeloid leukemia (Bonnet and Dick, 1997). Researchers found that although there are many different populations of cells within a tumor, only one population has the ability to generate the tumor. This was determined by separating the populations from each other and engrafting them into an immuno-compromised (NOD/SCID) mouse; the population identified as CSCs was able to recreate the original tumor, including morphology and the specific differentiated cell types observed within the tumor (Vermeulen et al., 2008).

The different populations within a tumor can be separated and identified according to the proteins expressed (or produced) on the surface of a particular cell; cells expressing the same set of proteins are grouped into one population. Because such proteins are commonly used to identify and categorize cells, they are called cell markers. CSCs from the same tumor type usually have the same set of markers expressed, although the markers expressed can vary much more between CSCs from different tissues (Vermeulen et al., 2008). For example, breast cancer CSCs have been found to express a marker called CD44, but are distinct for also not expressing the marker CD24 (making this CSC population be labeled CD44+/CD24) (Al-Hajj et al., 2002). In comparison, pancreatic cancer CSCs express CD44, but also express CD24 (Li et al., 2007). Although there are differences like this in marker expression between CSCs from different tumor types, some markers are present in CSCs from many different types of tumors, such as CD44. CSCs from ovarian tumors (Zhang et al., 2008) and head and neck squamous cell carcinomas (Prince et al., 2006) have also been found to express CD44. Another major marker protein expressed in CSCs across tissue types is CD133; it is expressed by CSCs found in brain (Singh et al., 2003), prostate (Lang et al., 2008), colon (O’Brien et al., 2007), lung (Eramo et al., 2007), and hepatic (Suetsugu et al., 2006) tumors. For a more detailed summary of marker expression of CSCs from the different tumors they have been discovered in, see Table 1.

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Table 1. Cancer Stem Cell Populations Detected in Different Cancerous Tumors (CSC Markers and Percent of the Total Tumor)

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