Journal
CELL
Volume 173, Issue 3, Pages 634-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.02.061
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Funding
- National Key Basic Research Program of China [2014CB542102]
- National Natural Science Foundation of China [81622023, 91542204, 81671564, 81422037, 81788101]
- CAMS Innovation Fund for Medical Sciences [2016-12M-1-003]
- National 135 Major Project of China [2017ZX10102032-002, 2018ZX10302205]
- MRC [G1001046, MC_UU_00008/11, G0600520, MR/L018942/1] Funding Source: UKRI
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Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, howprimary tumor-induced non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119(+)CD45(-)CD71(+) phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor arteminintothe blood. Transforming growth factor beta (TGF-beta) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells' tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications.
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