Taken together, the present study demonstrates a critical role for ETS transcription factors on VPC number and function. In vitro and in vivo high glucose levels increased ETS DNA-binding and thus most likely transcriptional activity. Inhibition of ETS1 and ETS2 expression counteracts the reduction of VPC number by enhancing endothelial lineage commitment. Given the fact that ETS transcription factors regulate a plethora of genes, a systematic analysis of other downstream targets besides CD115, MMP9, CD144 and CD105 investigated here is required to fully understand the role of the ETS family in the cardiovascular system. The growth of solid tumors is strongly influenced by its microenvironment. Besides well-studied microenvironmental parameters, such as hypoxia and angiogenesis,ML-7 hydrochloride mechanical stresses also play an important role. For a solid tumor to grow in a confined space defined by the surrounding tissue, it must overcome the resulting compressive forces. It has been shown that tumors and their associated stroma are mechanically stiffer than the corresponding normal host tissue, and that mechanical compression in such an environment can collapse blood and lymphatic vessels. However, our understanding of how this compression directly influences tumor growth is limited. Various hypotheses have been proposed regarding the involvement of mechanical stresses in tumor development, and Helmlinger et al. conducted the first quantification of spheroid growth inhibition in agarose gels. They also showed that such inhibition of tumor growth can be reversed by releasing the spheroids from the gel. Yet several key questions remain unanswered, including: What is the nature of the stress field around growing tumor spheroids? Can local solid stress distribution affect the shape of tumor spheroids? Does solid stress distribution also affect cell phenotype in different regions of individual spheroids? What is the intracellular pathway that regulates the solid stress-induced phenotypic change? In this study, we show that the accumulating solid stress in agarose gels around growing tumor spheroids can be measured using co-embedded fluorescent micro-beads as markers for strain in the gel: agarose gels are resistant to SGC0946 degradation by cancer cell proteinases, and thus allow studies of solid stress accumulation independent of cell invasion. We demonstrate that the shape of the solid stress field dictates the shape of tumor spheroids and that this effect is due to suppression of cell proliferation and induction of cell apoptosis in regions of high solid stress. Finally, we elucidate the molecular mechanism for the solid stress-induced apoptosis. The present study addressed several remaining questions concerning the effect of compressive stress on the growth dynamics of solid tumors. Although empirical mathematical models such as the well-known Gompertzian growth curve and the more recent ‘‘universal growth law’’ can predict the enlargement of many solid tumors with good accuracy, they do not explicitly consider cell dynamics inside the tumors. In particular, the invariable emergence of a plateau phase after tumors have reached a certain size has never been satisfactorily explained. As most solid tumors larger than 1 mm in diameter induce angiogenesis, nutrient or oxygen depletion should not limit tumor growth.