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Tumor cell lines do not form a homogenous entity - monoclonal but heterogeneous

Tumor cell lines are not homogeneous cell populations. Experiments with SCLC cells suggest (at least) two possibilities:

The "fractal model": The total cell population consists of single cells with varying doubling times (hours to weeks). However, each single cell is able to regenerate the entire pattern of varying doubling times through successive cell divisions (Fig. 4A). This is analogous to the self-similarity of fractals.

The "non-classical stem cell model": The whole cell population consists of two subpopulations that can be generated, at least partially, from each other via cell division. The first one divides quickly and possesses a limited proliferation potential, whereas the second one divides slowly but indefinitely. In the context of a linear stem cell model the first subpopulation corresponds to "transient amplifying cells", the second one to "classical stem cells" (Fig. 4B).

Figure 4A: Fractal model - In the entire population, individual cells divide with different rates (here shown as a Gaussian distribution). From the descendants of a single cell, the entire variations in doubling times can be regenerated.

Figure 4B: Non-classical stem cell model - cell lines consist of two subpopulations that differ in their replication potential (limited vs. unlimited.) and their doubling time (fast vs. slow). During cell division, a daughter cell may gain properties of the other subpopulation, in particular, it may develop into a secondary stem cell (red ellipse). This possibility is not considered in the classical stem cell model.


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