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. 2016 Oct;6(10):363.
doi: 10.4172/2157-7633.1000363. Epub 2016 Oct 26.

Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance

Gina Lee  1 , Robert R Hall 3rd  1 , Atique U Ahmed  1
Affiliations

Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance

Gina Lee et al. J Stem Cell Res Ther. 2016 Oct.

Abstract

Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and disease progression. This theory hypothesizes that a population of the tumor cell with similar functional and phenotypic characteristics as normal tissue stem cells are responsible for formation and advancement of many human cancers. The CSCs subpopulation can differentiate into non-CSC tumor cells and promote phenotypic and functional heterogeneity within the tumor. The presence of CSCs has been reported in a number of human cancers including blood, breast, brain, colon, lung, pancreas prostate and liver. Although the origin of CSCs remains a mystery, recent reports suggest that the phenotypic characteristics of CSCs may be plastic and are influenced by the microenvironment specific for the individual tumor. Such factors unique to each tumor preserve the dynamic balance between CSCs to non-CSCs cell fate, as well as maintain the proper equilibrium. Alternating such equilibrium via dedifferentiation can result in aggressiveness, as CSCs are considered to be more resistant to the conventional cancer treatments of chemotherapy and radiation. Understanding how the tumoral microenvironment affects the plasticity driven CSC niche will be critical for developing a more effective treatment for cancer by eliminating its aggressive and recurring nature that now is believed to be perpetuated by CSCs.

Keywords: Cancer stem cells; Cellular plasticity; Niche; Tumor cells.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Hierarchy leading to heterogeneity. The CSC theory claims that CSCs arise from normal stem cells within the population and that only these CSCs drive tumorgenesis. These CSCS can either self renew or divide into differentiated progeny. Since the cells in a tumor come from different CSCs, the tumor is heterogenic.
Figure 2
Figure 2
Asymmetric division of CSCs. (A) Asymmetric cellular division yields one undifferentiated CSC and one differentiated cell. Under normal conditions, this is the second most common division, but during TMZ treatment this type of division occurs least. (B) Symmetric cell renewal produces two daughter CSCs that are identical to the mother CSC. Under normal conditions, this is the least observed division, but becomes the most prevalent when the population is treated with TMZ. This largely contributes to the resistance and reoccurrence of tumors. (C) Symmetric differentiation yields two differentiated progeny. Under normal conditions, this division occurs most frequently. However, during TMZ treatment, this division is seen second most often.
Figure 3
Figure 3
CSC, microenvironment and intratumoral equilibrium. When a tumor is exposed to hypoxia, low pH, chemotherapy or radiation, a microenvironment that favors CSCs is created. Because of this, some mature cells in the tumor dedifferentiate and stemness in the present CSCs is maintained. This plasticity of the tumor leads to drug resistance and disease reoccurrence.
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