0000000000117430
AUTHOR
Mathias Ritter
Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR
Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, l…
Ex Vivo Retinal Explant Cultures to Study Angiogenic Responses
The mouse retina has long been regarded as an easily accessible and advantageous system to investigate important questions of developmental angiogenesis. The protocol presented here profits from the suitability of the mouse retina as experimental model and describes an ex vivo culture technique of mouse retina explants that allows the quantitative assessment of angiogenic responses to pharmacological manipulations. The technique involves the extraction of the retina from the intact eye, the immediate flat mounting of the tissue on a hydrophilic membrane and the acute stimulation or inhibition of angiogenic processes of the developing vessels in their physiological context ex vivo. The numbe…
Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system.
Developing the bloodbrain barrier During development, signals need to be dynamically integrated by endothelial cells, neurons, and glia to achieve functional neuro-glia-vascular units in the central nervous system. During cortical development, neuronal Dab1 and ApoER2 receptors respond to a guidance cue called reelin. Studying mice, Segarra et al. found that Dab1 and ApoER2 are also expressed in endothelial cells (see the Perspective by Thomas). The integration of reelin signaling in endothelial cells and neurons facilitates the communication between vessels, glia, and neurons that is necessary for the correct positioning of neurons during cortical development. This integration is also impo…