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Cancer Stem Cells
(Lay)
Stem cells are defined as those that generate a mixture of progeny, including daughters that remain undifferentiated like their parent (undergo self renewal) and daughters that demonstrate terminal cell differentiation. Self renewal constitutes the ability to demonstrate an unlimited number of cellular divisions without differentiating, thereby ensuring chromosomal preservation. Terminal cell differentiation is the process in which a cell acquires its final specialized characteristics and permanently stops dividing. Therefore, when a stem cell divides each daughter cell has a choice: it can either remain a stem cell (undergo self renewal) or it can be committed to terminal cell differentiation. [See figure 1.]
Figure 1
Stem cells can give rise to (differentiate into) the many different cell types that make up the body, given the appropriate conditions or signals. Thus, different types of stem cells are specialized for the genesis of terminally differentiated cells. For example, epidermal stem cells for the epidermis, neural stem cells for brain tissue and cardiac stem cells for the heart, etc. Control of the cellular divisions resulting from stem cells is key to maintain an appropriate number of cells in a population at any given time. Most normal cells cease to divide when they mature into terminally differentiated and specialized cells, thereby resulting in a balance between genesis and destruction. However, if that balance is off it can result in abnormal cells. Two situations that lead to imbalance are as follows: [See figure 2.]
- More than 50% of daughter cells remain as stem cells.
- The process of differentiation is altered so that daughter cells retain the ability to divide indefinitely.
Figure 2- click for larger image
An example of a cell type that experiences the abnormalities discussed above is cancer cells. Cancer cells are believed to be associated with cancer stem cells which result from mutations of normal stem cells. The cancer stem cell hypothesis states "the cancer-initiating cell is a transformed tissue stem cell, which retains the essential property of self-protection through the activity of multiple drug resistance (MDR) transporters. This resting constitutively drug-resistant cell remains at low frequency among a heterogeneous tumor mass." Hence the mutation allows for unbridled cell growth and resistance to chemotherapeutic efforts. Current cancer therapies focus on shrinking the tumor size however that approach may not necessarily eradicate the cancer stem cell. [See figure 3.]
Figure 3: WRONG TARGET. Traditional cancer therapies (top) kill rapidly dividing tumor cells (red) but may spare stem cells (blue) that can give rise to a new tumor. In theory, killing cancer stem cells (bottom) should halt a tumor's growth and perhaps even lead to its disappearance.
Acknowledgements
This review was prepared by the following graduate students in the Stem Cell Biology Class, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey:
Brian Baker, Ioana Vlad, Jennifer Barbre, Michelle Moh, Ru Chen, Sarah Bliss
Teaching Assistant: Elaine Wong
The review was edited by two stem cell biologists.
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