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FIGURE 7.5
Results from Wilkinson et al. [36], showing in vivo inhibition of Aurora B
kinase using the novel agent AZD1152. Nude mice bearing SW620 colon cancer xenografts
were treatedwith drug for 48 h and the tumors excised, disaggregated, and dual stained for DNA
content and phosphorylated histone H5. Note the loss of P-H3 in the treated tumor, which is
associated with a polyploidy DNA content, consistent with Aurora B kinase inhibition.
for acetylated histones, this paper does illustrate the future potential for flow
cytometry techniques to study histone modifications and the effects of newer drugs
that selectively modify them.
7.3.4 Rare Event Detection and Analysis: Cancer Stem Cells
The ability to make measurements in rare subpopulations of cells has long been
recognized as one of the unique strengths of flow cytometry. This has been reem-
phasized in recent years with the renewed interest in cancer stem cells, which are
believed to represent a small but critical subpopulation in many types of cancer.
Although there is some controversy as towhether they are true stem cells, there is now
an extensive literature showing that human cancers can be grown from a limited
number of cancer cells, viably flow sorted based on the surface expression of putative
stem cell markers such as CD133, and that the tumors formed recapitulate the
phenotypic heterogeneity seen in the original specimen, whereas the bulk cancer cell
population is not able to initiate cancers when implanted into immune-deprived
mice [1, 2, 41]. At the present time, cancer-initiating (or stem) cells are defined by
their ability to grow tumors at limiting dilution rather than by an unambiguous
immunophenotype. However, further progress in this field should allow the devel-
opment of more sophisticated flow cytometry protocols combining intracellular
markers to study their biology with respect to drug treatment. Importantly, several
reports suggest that this subpopulation of cancer-initiating cells can be resistant to
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