Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype

Cell Rep. 2016 Jul 26;16(4):917-927. doi: 10.1016/j.celrep.2016.06.058. Epub 2016 Jul 14.


The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

MeSH terms

  • Animals
  • Antigens / metabolism*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Lineage / physiology
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Male
  • Mesoderm / metabolism*
  • Mesoderm / pathology
  • Mice
  • Mice, Knockout
  • Mutation / physiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Pericytes / metabolism*
  • Phenotype
  • Proteoglycans / metabolism*
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / metabolism
  • beta Catenin / metabolism*


  • Antigens
  • Chondroitin Sulfate Proteoglycans
  • Proteoglycans
  • Tumor Suppressor Protein p53
  • beta Catenin
  • chondroitin sulfate proteoglycan 4