Questions on Cancer Research

The following question/answer section is part of our Evolution Grid-Computing Project. They all deal with an article we read entitled, “Normal Stem Cells and Cancer Stem Cells: The Niche Matters” by Li and Neaves (2006).

1. In your interview, the oncology nurse agreed that stem cells may be the key to eradicating cancer. This article addresses this perspective as well as its antithesis, as it discusses the role of stem cells in cancer causation. It states that as few as 1 to 2 mutations can change a stem cell into a cancer cell. Remembering that mutations generate variation, how is cancer an evolutionary phenomenon?

The article talks about how somatic cells have to undergo six different mutations in order to become cancerous. This is different from stem cells which only have to undergo two mutations to become cancerous. Based on the principle of Ockham’s Razor, the simplest path is the correct path. This would mean that it is most likely that stem cells are the cells that become cancer cells because it is probably that a population of cells in an individual would undergo two mutations rather than six. Mutation is a form of evolution and if stem cells mutate into cancer cells, more cancer cells will be produced. However the evolution is occurring within an individual. If stem cells mutate into cancer cells, those cells will divide and produce more cancer cells. This will generate variation among the population of cells within an organ.

2. Most genes code for proteins. Given the information in this article and the above question, why is it important to look at protein folding and mis-folding when studying cancer?

By studying and understanding protein folding and mis-folding, researchers believe we can find the cure to many diseases, cancer being one, for example. Thus far this semester we have been involved in a grid-computing project. The efficiency of grid-computing is tremendous and enables many corporations, research teams, and everyday volunteers at home to use cutting-edge technology to aid in information processing. By participating in grid-computing and folding at home projects, everyday people are able to see the significance of protein folding and the consequences of mis-folding. Mis-folding is the result of an error in the genetic blueprint which leads to incomplete folding of that particular protein, which ultimately affects its function. As described in the paper, tumorigenesis is the result of mutations that interfere with the appropriate function of regulatory proteins. This deals with cancer in that tumor suppressors become inactive and lead to cancer as a loss of function phenotype. Therefore, by studying mis-folding of proteins and comparing normal protein folding, researchers can see what mutations are occurring and why. This can lead to more insightful information about cancer’s development and perhaps a cure.

3. In an evolutionary sense, why is it informative to study cancer and its implications in flies or, especially, in mice?

Mice and flies are inexpensive and easy to handle and so are often used in experiments. Also flies and mice reproduce quickly and many generations can be observed. Also there are no laws protecting mice and flies so researchers can do any sort of test without having to document the animals’ safety. There have been several experiments done with mice that have proven that stem cells play a part in perpetuating cancer in organs such as the breasts and the brain. In observing generations of flies and or mice one can see the heritability in cancer and see if cancer undergoes evolution. It is especially informative when studies are done on mice because they have a genome that is closer to ours as humans and we can conclude that the cancer that is observed in mice will react similar to human cancers. Orthology refers to genes in different species that derive from a common ancestor and can be applied to mice and humans. However, these orthologous genes may or may not have the same function.

4. What is a niche in the context of an ecosystem? Is the stem cell “niche” similar, in that different niches impose different selection pressures on the stem cells? Explain how niche control of stem cells is like natural selection.

In terms of an ecosystem, a niche describes how an organism or population responds to the distribution of resources and competitors. A stem cell niche is a special environment in which stem cells reside. The stem cell niche sends signals to the stem cells to inhibit or promote proliferation. We know that stem cells are dependant on the niche because when the niche is lost many stem cells are lost. There are special adhesion molecules that connect a stem cell to its niche. The niche is hypothesized to control stem cells and when they should divide. Niche control is like natural selection because the niche can control which stem cells to divide. Just like natural selection can show selection for or against an allele, the niche can show selection for healthy stem cells or cancerous stem cells to divide and reproduce.