C5: Vascular control of tumor progression and metastasis
Seeded metastatic cells interact in a dynamic bi-directional manner with endothelial cells (EC) in the metastatic niche. Moreover, primary tumor-derived factors including secreted factors as well as exosomes may in a systemic manner also interact with EC at distant sites to induce transcriptomic changes that establish a pre-metastatic niche before metastasizing tumor cells have arrived at the distant site. Employing surgical metastasis models, we have in preliminary experiments performed a systematic analysis of the transcriptomic changes in EC in the pre-metastatic and metastatic lung EC niches by performing bulk RNA-seq experiments of ultra-pure freshly isolated EC in tumor bearing mice at different stages of primary tumor and metastatic growth. Building on these preliminary proof-of-concept experiments the present project is aimed at systematically deciphering EC transcriptomic and epigenetic changes in the EC pre-metastatic and metastatic niches pursuing a systems biology approach.
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High resolution image analysis of tumor cell-EC interaction
during metastatic seeding