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

• Published in: Cell reports (Cambridge) Vol. 16; no. 4; pp. 917 - 927
• Main Authors: Sato, Shingo, Tang, Yuning J., Wei, Qingxia, Hirata, Makoto, Weng, Angela, Han, Ilkyu, Okawa, Atsushi, Takeda, Shu, Whetstone, Heather, Nadesan, Puvindran, Kirsch, David G., Wunder, Jay S., Alman, Benjamin A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2016; Elsevier
• Subjects: Animals; Antigens - metabolism; beta Catenin - 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
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.06.058

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. [Display omitted] •Pericytes can be a cell of origin for benign and malignant mesenchymal neoplasms•Malignant sarcomas show a decrease in β-catenin signaling compared to pericytes•Benign desmoids show an increase in β-catenin signaling compared to pericytes Sato et al. use lineage-tracing studies in mice to show that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor gene can derive from Ng2/Cspg4-expressing pericytes. Their data show that pericytes can be a cell of origin for mesenchymal tumors and that β-catenin plays a critical role in mesenchymal neoplasia.