Sampling from single-cell observations to predict tumor cell growth <i>in-vitro</i> and <i>in-vivo</i>.
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Abstract | :
Cancer stem-like cells (CSCs) are a topic of increasing importance in cancer research, but are difficult to study due to their rarity and ability to rapidly divide to produce non-self-cells. We developed a simple model to describe transitions between aldehyde dehydrogenase (ALDH) positive CSCs and ALDH(-) bulk ovarian cancer cells. Microfluidics device-isolated single cell experiments demonstrated that ALDH+ cells were more proliferative than ALDH(-) cells. Based on our model we used ALDH+ and ALDH(-) cell division and proliferation properties to develop an empiric sampling algorithm and predict growth rate and CSC proportion for both ovarian cancer cell line and primary ovarian cancer cells, in-vitro and in-vivo. In both cell line and primary ovarian cancer cells, the algorithm predictions demonstrated a high correlation with observed ovarian cancer cell proliferation and CSC proportion. High correlation was maintained even in the presence of the EGF-like domain multiple 6 (EGFL6), a growth factor which changes ALDH+ cell asymmetric division rates and thereby tumor growth rates. Thus, based on sampling from the heterogeneity of in-vitro cell growth and division characteristics of a few hundred single cells, the simple algorithm described here provides rapid and inexpensive means to generate predictions that correlate with in-vivo tumor growth. |
Year of Publication | :
2017
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Journal | :
Oncotarget
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Volume | :
8
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Issue | :
67
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Number of Pages | :
111176-111189
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Date Published | :
2017
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URL | :
http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=22693
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DOI | :
10.18632/oncotarget.22693
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Short Title | :
Oncotarget
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