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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sato, S; Tang, YJ; Wei, Q; Hirata, M; Weng, A; Han, I; Okawa, A; Takeda, S; Whetstone, H; Nadesan, P; Kirsch, DG; Wunder, JS; Alman, BA

Published Date

  • July 14, 2016

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 917 - 927

PubMed ID

  • 27425618

Pubmed Central ID

  • 27425618

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

International Standard Serial Number (ISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2016.06.058

Language

  • eng