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Do cancer cells undergo phenotypic switching? The case for imperfect cancer stem cell markers.

Zapperi S, La Porta CA - Sci Rep (2012)

Bottom Line: Here we explore an alternative explanation based on the hypothesis that markers are not perfect and are thus unable to identify all cancer stem cells.Our analysis is based on a mathematical model for cancer cell proliferation that takes into account phenotypic switching, imperfect markers and error in the sorting process.Our conclusion is that the observation of reversible expression of surface markers after sorting does not provide sufficient evidence in support of phenotypic switching.

View Article: PubMed Central - PubMed

Affiliation: CNR-IENI, Via R. Cozzi 53, 20125 Milano, Italy. stefano.zapperi@cnr.it

ABSTRACT
The identification of cancer stem cells in vivo and in vitro relies on specific surface markers that should allow to sort cancer cells in phenotypically distinct subpopulations. Experiments report that sorted cancer cell populations after some time tend to express again all the original markers, leading to the hypothesis of phenotypic switching, according to which cancer cells can transform stochastically into cancer stem cells. Here we explore an alternative explanation based on the hypothesis that markers are not perfect and are thus unable to identify all cancer stem cells. Our analysis is based on a mathematical model for cancer cell proliferation that takes into account phenotypic switching, imperfect markers and error in the sorting process. Our conclusion is that the observation of reversible expression of surface markers after sorting does not provide sufficient evidence in support of phenotypic switching.

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Related in: MedlinePlus

Growth curves.Using the same parameters employed in Fig. 7 one can also reproduce with phenotypic switching and imperfect marker models the growth curves of the two subpopulations. The differences between the two models appear only at long times (inset).
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f8: Growth curves.Using the same parameters employed in Fig. 7 one can also reproduce with phenotypic switching and imperfect marker models the growth curves of the two subpopulations. The differences between the two models appear only at long times (inset).

Mentions: In order to get more insight on the process underlying the observed behavior one can consider the growth curves of the sorted subpopulations. The experimental data reported in Ref. [4] refer to two days of growth and show no significant difference in proliferation between sorted subpopulations. This observation was considered in Ref. [4] as additional evidence in favor of phenotypic switching. This is, however, not the case as shown in Fig. 8 which compares the experimental data with the prediction of the phenotypic switching and imperfect marker models. Both models show no difference in growth at short times, while the difference can only be observed at later times. A similar result was reported for melanoma cells sorted with a putative stem cell marker (ABCG2)11: a difference in the growth for positive and negative cells was observed only after two months of cultivation.


Do cancer cells undergo phenotypic switching? The case for imperfect cancer stem cell markers.

Zapperi S, La Porta CA - Sci Rep (2012)

Growth curves.Using the same parameters employed in Fig. 7 one can also reproduce with phenotypic switching and imperfect marker models the growth curves of the two subpopulations. The differences between the two models appear only at long times (inset).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369193&req=5

f8: Growth curves.Using the same parameters employed in Fig. 7 one can also reproduce with phenotypic switching and imperfect marker models the growth curves of the two subpopulations. The differences between the two models appear only at long times (inset).
Mentions: In order to get more insight on the process underlying the observed behavior one can consider the growth curves of the sorted subpopulations. The experimental data reported in Ref. [4] refer to two days of growth and show no significant difference in proliferation between sorted subpopulations. This observation was considered in Ref. [4] as additional evidence in favor of phenotypic switching. This is, however, not the case as shown in Fig. 8 which compares the experimental data with the prediction of the phenotypic switching and imperfect marker models. Both models show no difference in growth at short times, while the difference can only be observed at later times. A similar result was reported for melanoma cells sorted with a putative stem cell marker (ABCG2)11: a difference in the growth for positive and negative cells was observed only after two months of cultivation.

Bottom Line: Here we explore an alternative explanation based on the hypothesis that markers are not perfect and are thus unable to identify all cancer stem cells.Our analysis is based on a mathematical model for cancer cell proliferation that takes into account phenotypic switching, imperfect markers and error in the sorting process.Our conclusion is that the observation of reversible expression of surface markers after sorting does not provide sufficient evidence in support of phenotypic switching.

View Article: PubMed Central - PubMed

Affiliation: CNR-IENI, Via R. Cozzi 53, 20125 Milano, Italy. stefano.zapperi@cnr.it

ABSTRACT
The identification of cancer stem cells in vivo and in vitro relies on specific surface markers that should allow to sort cancer cells in phenotypically distinct subpopulations. Experiments report that sorted cancer cell populations after some time tend to express again all the original markers, leading to the hypothesis of phenotypic switching, according to which cancer cells can transform stochastically into cancer stem cells. Here we explore an alternative explanation based on the hypothesis that markers are not perfect and are thus unable to identify all cancer stem cells. Our analysis is based on a mathematical model for cancer cell proliferation that takes into account phenotypic switching, imperfect markers and error in the sorting process. Our conclusion is that the observation of reversible expression of surface markers after sorting does not provide sufficient evidence in support of phenotypic switching.

Show MeSH
Related in: MedlinePlus