Thursday, April 20, 2006

Cancer Stem Cells

Event: Robert Weinberg
Date: Tuesday, April 18, 2006
Time: 4:30 PM to 6:00 PM

This talk was on cancer stem cells, a topic very pertinent to my research. The beginning of the talk was on basic cancer information, which made it very obvious that it was occurring at an undergraduate venue (Amherst College). He did reaffirm a few numbers for me though, such that a cell can only split a max of about 50 times and that that probability for mutation is very low (at most 1 in 1x10^6 according to him).

The later part of the talk was actually on stem cells, and was interesting after we got past the description of what the different types were (stem, progenitor, differentiated). Apparently it is possible to separate stem and non-stem cells from a group by the proteins they each have on their surface. The stem cell will have a different type from the other ones. So, you can bind a die to an antigen that will bond with only the stem cell protein, and then bind dies to antigens that bond with the other cells' proteins, and use light refraction to see the different colors and separate them out. That is very interesting for both cancer and regular medical/biological research.

Also interesting was a discussion on whether or not tumors are organized hierarchically like regular cells are. In regular sets of cells, we have stem cells that are a sort of "super parent" in the fact that they can create any type of cell (most people would know this just from the regular news). These cells can create progenitor cells (he called them "transit-amplifying cells" and I like to call them "blast cells") that are capable of differentiating into a specific type of cell. The children of blast cells eventually become differentiated cells, which are basically a mature cell that will not change its function during its lifetime. Blast cells can also create more blast cells, and when stem cells split they create a new copy of themselves (so that there is one blast cells and one stem cell). Originally it was assumed that tumors were only made of mature cells, and that stem cells did not exist in a tumor as stem cells are less likely to mutate. There was speculation that a tumor cell might incur a change that turned it into a tumor stem cell, however.

So, at this talk he described a study showing that tumor stem cells did indeed exist. A group apparently split apart tumor cells the same way that regular cells were split apart, using antigens. Tumor initiating cells appear to be a small minority, which is a property of stem cells. This makes sense, as other cells would be unable to split enough times to form a proper tumor, although personally I'm not sure that limit would still be in place in a tumor cell. When an experiment was done with the separated cells, however, it was found that the cells they thought were stem cells could create a tumor in a mouse if only 200 of them were implanted whereas 20,000 of the others failed to form a tumor when implanted. Usually researchers implant 100,000's of cells to get a tumor growing, so it is interesting that only 200 of a specific type would be necessary. This experiment is why many agree that tumors do have stem cells.

One implication from the existence and ability of tumor stem cells involves metastasis, which is when a tumor migrates to another part of the body or tissue to become cancer. If only tumor stem cells are capable of growing a tumor, would only tumor stem cells be involved in metastasis? If so, could we stop metastasis by killing the stem cells?

There are still many things that are not known though. For instance, no one is sure if regular stem cells are likely to become tumor stem cells. Since stem cells don't replicate often and the majority of mutations are going to occur due to replication (or at least be spread by it), it seems unlikely. Most people currently assume that progenitor cells are the ones that become tumor stem cells, as they are only slightly different from stem cells to begin with.

There are treatments out there (he named "Gleevac") that can kill off all of the tumor except the stem cells. So once you stop with the treatment, the tumor is just replenished from the stem cells. Companies would like to make a treatment to kill the tumor stem cells, but no one can figure out how to do that without killing the healthy stem cells as well (which would probably kill you in the end, as the body is constantly killing and replenishing cells). The reason the current treatment doesn't work is that it ruins a cell's DNA, and cells that split frequently end up dying because they can't fix their genes in time to split. However, stem cells don't replicate frequently, so they are able to repair the damage before splitting.

So if we can research tumors in a similar way to regular cell growths, and figure out how to get rid of those stem cells, we've cured cancer! Which of course is easier said than done.

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