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oai:repisalud.isciii.es:20.500.12105/179722024-11-29T23:21:42Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Ghajar, Cyrus M author Peinado, Héctor author Mori, Hidetoshi author Matei, Irina R author Evason, Kimberley J author Brazier, Hélène author Almeida, Dena author Koller, Antonius author Hajjar, Katherine A author Stainier, Didier Y R author Chen, Emily I author Lyden, David author Bissell, Mina J author 2013-07 In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth. Nat Cell Biol . 2013 ;15(7):807-17. 10.1038/ncb2767 1476-4679 Nature cell biology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826912/ 23728425 http://hdl.handle.net/20.500.12105/17972 The perivascular niche regulates breast tumour dormancy.