Deciphering Fate Decision in Normal and Cancer Stem Cells: Mathematical Models and Their Experimental Verification - Mathematical Methods and Models in Biomedicine - page 214

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Dkk1 Concentration (ng/ml)

Fig. 6 Effect of Dkk1 treatment on mammosphere formation. Dkk1 effect was measured by
MCF-7 cells ( dark grey bars ) and by primary human invasive breast cancer cells ( bright grey bars ).
MCF-7 cells were pre-incubated with graded concentrations of Dkk1 in serum-free medium for
24 h and then plated for mammosphere-forming assays for 7 days. Primary breast cancer cells
were plated in the presence of Dkk1 and cultured for 7 days. Data for each concentration of
Dkk1 are expressed as the fold change in mammosphere formation compared to untreated controls
(0 ng/mL). Asterisks mark statistically significant differences [ 5 ]

exogenous Dkk1 can be used to control the number of SCs transitioning from
proliferation to differentiation and thus to maintain tissue homeostasis, even in
situations of derangement of the intracellular mechanism controlling SC fate
decision.

6.4 Experimental Validation in Breast Cancer Stem Cells

To test model predictions, in vitro experiments on breast cancer MCF-7 cell line,
and on primary cells from breast cancer patients, were conducted [ 5 ]. Agur and
colleagues treated these cell colonies with graded doses of Dkk1 and measured
each dose's effect on the proportion of breast cancer cells characterized by the
SC phenotype CD 44 + CD 24 −/ low [ 6 , 33 ] and on mammosphere formation [ 33 ].
For both the cell line and primary breast cancer cells, the results validated the
model prediction that high Dkk1 levels would reduce the number of CSCs. This
is demonstrated in Fig. 6 , where mammosphere formation under high Dkk1 levels is
shown to decrease in a dose-dependent manner. At low levels of Dkk1, there was no
increase in CSC numbers or mammosphere formation in primary breast cancer cells,
but there was a significant increase in the number of CSCs observed for MCF-
7 cells. Overall, the results were variable and highly dependent on the particular