All Things Stem Cell

Teisha J. Rowland, the author of All Things Stem Cell, recently started a general biology column with The Santa Barbara Independent. This new column, titled “Biology Bytes,” will have weekly stories posted on a wide variety of biology topics, so far ranging from snails, marsupials, and parrots, to stem cells.

The most recent article, “Likely Suspects in Cancer Growth,” is on cancer stem cells — it is a modified version of the “All Things Stem Cell” post “Cancer Stem Cells: A Possible Path to a Cure” to fit a more lay public audience.

Tune in to “Biology Bytes” for weekly stories on a wide array of fascinating biology topics, including more accessible explanations of stem cell biology.

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Recently, many papers have come out that highlight connections between cancer and induced pluripotent stem cells (iPSCs), the latter of which was discussed previously. These papers hold many implications for not only iPSCs, but for our understanding of cancer as well. Additionally, these papers should not at all be thought of as invalidating the importance of iPSCs for studying and treating future therapies, but they should help us better understand what iPSCs are and how to use them appropriately.

The most recent and most publicized link between iPSCs and cancer is p53. p53, also known as protein 53 (53 referring to its molecular mass), is a well-studied protein whose normal function is important in preventing cancer. Though p53 has many different roles, they are quite related. In essence, the job of p53 is to make sure the cell does not accumulate DNA damage, or DNA mutations, which could eventually make the cell cancerous. When a cell has its DNA damaged, often from external stresses, p53 stops the normal cell cycle to fix the DNA damage. If the damage is too great to repair, p53 can prevent the cell from dividing, which would create more damaged cells; p53 initiates programmed cell death, or apoptosis. The potential tumor cell dies. Overall, p53 functions as a “tumor suppressor” to prevent abnormal cells from occurring and multiplying into a cancer (Vazquez et al., 2008). Consequently, it has been found that p53 is mutated in approximately 50% of all human tumors, and other tumors may have mutations in the pathway regulating p53 activity (Vazquez et al., 2008). p53 is therefore well-studied as an oncogene, or a gene that when not functioning normally can contribute to a normal cell becoming cancerous.

So what does p53 have to do with iPSCs? One recently discovered connection is with the generation of iPSCs. Recently, many research groups discovered that when p53 is deleted from, or damaged in, their cells, they could more easily become iPSCs (Hong et al., 2009; Kawamura et al., 2009; Utikal et al., 2009; Li et al., 2009; Zhao et al., 2008). As posted earlier, iPSCs are cells that were originally from adult tissues, but have been “reprogrammed” to be pluripotent stem cells, or stem cells able to become all the adult cells of the body, looking and functioning nearly identical to human embryonic stem cells (hESCs) (Takahashi et al., 2007; Yu et al., 2007).

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admin Cancer Stem Cells, Embryonic Stem Cells, Induced Pluripotent Stem Cells adult, cancer, embryonic, news, regenerative medicine

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.

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

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