| Abstract | We set out to investigate the emerging intratumoral heterogeneity and to determine the evolutionary trajectories of the combination of cell-intrinsic kinetics that yield aggressive tumor growth . |
| Abstract | Our study suggests that cell proliferation potential is the strongest modulator of tumor growth . |
| Author Summary | We present an in silico computational model of tumor growth and evolution according to the cancer stem cell hypothesis. |
| Introduction | Transformation may occur at any time in all tissue compartments, but the ability of transformed cells to initiate and sustain pathologic tumor growth requires certain kinetic properties including longevity, migration potential, self-renewal and differentiation capacity. |
| Introduction | The kinetics will be inherited by the descendent cells yielding tumor population dynamics ranging from microscopic dormancy to aggressive tumor growth [16]. |
| Spontaneous undirected mutations promote tumor growth | Spontaneous undirected mutations promote tumor growth |
| Spontaneous undirected mutations promote tumor growth | We initialize tumor growth simulations with one CSC with the initial traits probability of symmetric division ps 2 0.05, proliferation capacity p = 10, migration potential [.1 = 15 and probability of spontaneous death or = 0.01, which has previously been shown to simulate fast tumor growth [16,27]. |
| Spontaneous undirected mutations promote tumor growth | We simulate tumor growth for t = 730 days, i.e. |
| Abstract | Angiogenesis plays a key role in tumor growth and cancer progression. |
| Author Summary | Tumor vascularization is essential for tumor growth and cancer progression. |
| Combining computational and experimental approaches to delineate the pathways controlling TEM pro-angiogenic function | The identification of the ligands and the pathways controlling the highly pro-angiogenic activity of tumor TEM is of paramount significance because it represents the rationale for a treatment directing TEM away from being cells supporting tumor growth . |
| Introduction | The VEGFR-1 (Vascular Endothelial Growth Factor Receptor-1), TGFBR-l ( Tumor Growth Factor [3 Receptor-1), TNF-Rl (Tumor Necrosis Factor Receptor-1) pathways have been reported to regulate tumor angiogenesis [36,37], but their activities have not been examined in human TEM. |
| Supporting Information | Tumor tissue processing, TEM differentiation in vitro, TEM stimulation, in vitro angiogenesis assay, migration assay, tumor growth inhibition assay and protein profiling 81 Fig. |
| abundance of genes regulating differentiation and immune response of TEM differentiated in vitro | Taken together, our results suggest that ANG-2/TGF-[3 and PlGF/TGF-B treatments are not only anti-angiogenic but also shift the gene expression profile of monocytes toward the one of cells promoting immune surveillance, thereby limiting tumor growth . |