Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression

Cell. 2018 Apr 19;173(3):634-648.e12. doi: 10.1016/j.cell.2018.02.061. Epub 2018 Mar 29.


Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, how primary 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 artemin into the blood. Transforming growth factor β (TGF-β) 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.

Keywords: Ter-119; Ter-cell; artemin; cancer immunotherapy; erythroblast-like; hepatocellular carcinoma; prognosis biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / metabolism
  • Cell Movement
  • Cell Proliferation
  • Disease Progression*
  • Epithelial-Mesenchymal Transition
  • Erythroblasts / cytology*
  • Gene Expression Regulation, Neoplastic
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Hep G2 Cells
  • Humans
  • Leukocyte Common Antigens / metabolism
  • Leukocytes / cytology
  • Liver Neoplasms / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Invasiveness / genetics
  • Nerve Tissue Proteins / blood*
  • Signal Transduction
  • Spleen / cytology*
  • Transforming Growth Factor beta / metabolism*


  • ARTN protein, human
  • Artn protein, mouse
  • Gfra3 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Nerve Tissue Proteins
  • Transforming Growth Factor beta
  • Leukocyte Common Antigens
  • Ptprc protein, mouse