We show that subpopulations of cells purified for a given phenotypic state return towards equilibrium proportions over time. These observations can be explained by a Markov model in which cells transition stochastically between states. A prediction of this model is that, given certain conditions, any subpopulation of cells will return to equilibrium phenotypic proportions over time. A second prediction is that breast cancer stem-like cells arise de novo from non-stem-like cells. These findings contribute to our understanding of cancer heterogeneity and reveal how stochasticity in single-cell behaviors promotes phenotypic equilibrium in populations of cancer cells.
Now as we have discussed before, there is a widely held theory that cancer stem cells exist, they may be 1 in a million of them in a collection of other non-stem cancer like cells, and it is these few stem cells which control the growth of cancers.
There are two opposing theories:
1. Uniqueness of the Stem Cell: Namely that there are a few such cells and that they have the ability to reproduce albeit at a limited amount. They have malignant progeny which are not stem cell like. They are unique and one they are created they remain that way. The other malignant cells not stem cells remain as that.
2. Regeneration of Stem Cells: The second school as exemplified in this paper says that there seems to be a balance between percent of stem cells and percent cancerous but non-stem cells. That there may exist some mechanism o,f say inter cell signalling, which turns on and off stem like characteristics.
We would then ask one to consider our argument regarding prostate cancer. Say the HGPIN argument we made a few months ago. Namely, we know that HGPIN often moves to PCa. We also know that PCa may have a stem cell character. We know that there is a certain number of patients with HGPIN who undergo saturation biopsy who on second biopsies are found to no longer have any HGPIN. So where did ti go? Think stem cell, namely if one makes the following assumptions:
1. PCa has a stem cell
2. HGPIN is a precursor to PCa. It too may have a stem cell.
3. Saturation biopsy removes x% of the glands. x% removed contains y million cells.
4. If we calculate the probability of catching stem cells and we calculate the probability of catching all, given the density, then we can compare the percent HGPIN free of HGPIN on second biopsy and the probability of removing the stem cells. We get a close match.
Thus if this is projectable, then it may call into question the results in the breast cancer model. Namely if the stem cells are removed leaving only HGPIN with no stem cells, then the HGPIN regresses, is it from the loss of the stem cell AND the fact that the remaining HGPIN cannot regenerate them?
Interesting question.
Yet there is the more compelling issue of what pathways have been altered, what mechanism allows a non stem cell to become a stem cell. The observation has interest but without an underlying state model it lacks extensability.
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