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000179697 1001_ $$0P:(DE-He78)876d213ee6559a5e98ddf2113698ed0b$$aHongu, Tsunaki$$b0$$eFirst author$$udkfz
000179697 245__ $$aPerivascular tenascin C triggers sequential activation of macrophages and endothelial cells to generate a pro-metastatic vascular niche in the lungs.
000179697 260__ $$aLondon$$bNature Research$$c2022
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000179697 500__ $$a#EA:A010#LA:A010# / 2022 Apr;3(4):486-504
000179697 520__ $$aDisseminated cancer cells frequently lodge near vasculature in secondary organs. However, our understanding of the cellular crosstalk invoked at perivascular sites is still rudimentary. Here, we identify intercellular machinery governing formation of a pro-metastatic vascular niche during breast cancer colonization in the lung. We show that specific secreted factors, induced in metastasis-associated endothelial cells (ECs), promote metastasis in mice by enhancing stem cell properties and the viability of cancer cells. Perivascular macrophages, activated via tenascin C (TNC) stimulation of Toll-like receptor 4 (TLR4), were shown to be crucial in niche activation by secreting nitric oxide (NO) and tumor necrosis factor (TNF) to induce EC-mediated production of niche components. Notably, this mechanism was independent of vascular endothelial growth factor (VEGF), a key regulator of EC behavior and angiogenesis. However, targeting both macrophage-mediated vascular niche activation and VEGF-regulated angiogenesis resulted in added potency to curb lung metastasis in mice. Together, our findings provide mechanistic insights into the formation of vascular niches in metastasis.
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000179697 7001_ $$0P:(DE-He78)857b9409476ae7e0ab904637e739f88b$$aPein, Maren$$b1
000179697 7001_ $$0P:(DE-HGF)0$$aInsua-Rodríguez, Jacob$$b2
000179697 7001_ $$aGutjahr, Ewgenija$$b3
000179697 7001_ $$aMattavelli, Greta$$b4
000179697 7001_ $$0P:(DE-He78)5b11915b010a335eea3bb6401fdadb1f$$aMeier, Jasmin$$b5$$udkfz
000179697 7001_ $$0P:(DE-He78)c0ef7f4dc2506a8556df9214b1b713ba$$aDecker, Kristin$$b6
000179697 7001_ $$0P:(DE-He78)2a2525a03e926ea91ee9ac423bc8c7ba$$aDescot, Arnaud$$b7
000179697 7001_ $$0P:(DE-He78)3391c5ad790ea5359189d11f073fb103$$aBozza, Matthias$$b8$$udkfz
000179697 7001_ $$0P:(DE-He78)15dff5647002b4dcfe892b251cd14b62$$aHarbottle, Richard$$b9$$udkfz
000179697 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b10$$udkfz
000179697 7001_ $$00000-0003-2836-6699$$aSinn, Hans-Peter$$b11
000179697 7001_ $$0P:(DE-HGF)0$$aRiedel, Angela$$b12
000179697 7001_ $$0P:(DE-He78)ee36a00803235200292c3488043cfd68$$aOskarsson, Thordur$$b13$$eLast author$$udkfz
000179697 773__ $$0PERI:(DE-600)3005299-3$$a10.1038/s43018-022-00353-6$$n4$$p486-504$$tNature cancer$$v3$$x2662-1347$$y2022
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