Cancer Stem Cell Model
Tumor Evolution
Immune dysfunction, which is caused by the interaction of genetic factors and acquired environmental factors like a viral infection, keeps the body in a state of chronic, uncontrolled inflammation contributing to cancer growth and spread. This is called "mutation-selection-adaptation," and it happens as the tumor changes and grows. Also, the way tumors change will lead to the harmful effects of drug resistance transfer, so it is very important to understand how tumors change in order to develop better therapies in the clinic.
In the past, there have been two main approaches to explain how tumors grow: the stochastic clonal evolution model and the cancer stem cell (CSC) theory. In the stochastic clonal evolution model, each cell can be tumorigenic and keep the growth of the tumor going. In the cancer stem cell (CSC) theory, the tumor is organized in a hierarchy, and a subpopulation of cells keeps the growth going.
Fig.1 Unified model of tumor evolution. (Kreso, 2014)
Defining Stemness
To understand how cancer stem cells work, we need to know what makes normal stem cells different. A normal adult stem cell is a somatic cell that can divide many times and can give rise to both more stem cells and cells that specialize into other types of cells. Usually, the main jobs of a normal stem cell to do are: self-renew (for example, make more stem cells) and differentiate.
Fig.2 Stemness as a guiding principle that governs therapeutic response. (Kreso, 2014)
Cancer Stem Cells Model
Malignant tumors start in tissues with a cellular hierarchy made up of stem cells that live for a long time and keep dividing into progenitor cells and mature cells that only live for a short time. Self-renewal is a type of cell division that both healthy cells and at least some cancer cells do.
The cancer stem theory says that a small group of cancer cells are the only ones that can make a tumor grow and spread. Also, these cancer stem cells can give rise to cancer cells that are more differentiated and will stop multiplying or die because they can't go through mitosis anymore or can't do it at all. So, the cancer stem cell theory says that some parts of the normal cellular hierarchy are still present in many tumors.
There are two possible ways in which cancer stem cells can arise.
- Normal stem cells may serve as a source of cancer stem cells. Because leukemic cells are capable of differentiating into multiple mature cell lineages and the stem cells in acute leukemia share the expression of certain markers with normal stem cells. It was originally hypothesized that cancer stem cells arose from normal stem cells. However, this model suggests that mutations permit the uncontrolled expansion of cancer stem cells derived from normal stem cells.
- On the other hand, cancer stem cells develop from progenitor cells. Based on the discovery of new markers that enable the identification of progenitor cells capable of differentiating into mature blood cells but lacking the ability to self-renew, more recent evidence suggests that in many cancers, cancer stem cells arise from progenitor cells that have acquired the ability to self-renew.
Fig.3 The possible origins of cancer stem cells. (Lobo, 2007)
Table.1 Signaling pathways associated with normal stem cells and cancer stem cells. (Lobo, 2007)
References
- Kreso, A.; Dick, J.E. Evolution of the cancer stem cell model. Cell Stem Cell. 2014, 14(3): 275-279.
- Lobo, N.A; et al. The biology of cancer stem cells. Annual Review of Cell and Developmental Biology. 2007, 23: 657-699.
