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.
Bibliographical noteFunding Information:
5Institute of Microelectronics, Science and Engineering Research Council of the Agency for Science, Technology and Research, Singapore
This work was supported by the Ovarian Cancer Research Fund and the Department of Defense Ovarian Cancer Research Program Idea Award W81XWH-14-1-0187. UMCC core facilities are supported in part by the NIH through the UMCC Support Grant (P30 CA046592). RB is supported by NIH R01CA163345-05. AP is supported by NIH K08 DE026500-01.
© Pearson et al.
All Science Journal Classification (ASJC) codes