Abstract 4931: Cancer stem cells in solid tumors: Symmetric division, niche size, and invasive tumor morphology

Abstract

Abstract In recent years cancer stem cells have been identified as a minor subpopulation in numerous solid tumors that drives tumor initiation, development and metastasis. Although cancer stem cells have yet to be reliably isolated, populations enriched for tumor-initiating cells give an indication of the order of magnitude of the stem cells niche within primary tumors. Here we develop and discuss the predictions of a simple theoretical model of cancer stem cells and tumor growth dynamics. We evaluate the impact of cancer stem cell symmetric/asymmetric division and progeny cancer cell proliferation capacity on tumor progression and morphology. The model predicts that the frequency of symmetric cancer stem cell division determines the resulting stem cell pool size, and that the symmetric division frequency and the stem cell fraction are both typically small, consistent with the cancer stem cell hypothesis. At the same time, we show that intrinsic competition for space and environmental confinement can lead to an increasing stem cell fraction over time despite a fixed, low symmetric division probability. These findings offer a novel explanation for the apparent differences in reported stem cell numbers for different tumors as well as tumors of the same organ, and thus challenging the hypothesis of a fixed stem cell ratio for different tumors. The pivotal role of stem cell division strategies and stem cell ratio on spatio-temporal morphology evolution and self-organizing tumor patterning is discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4931. doi:10.1158/1538-7445.AM2011-4931