Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype.
Journal Article (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 26, 2016
Published In
Volume / Issue
- 16 / 4
Start / End Page
- 917 - 927
PubMed ID
- 27425618
Pubmed Central ID
- PMC4963269
Electronic International Standard Serial Number (EISSN)
- 2211-1247
Digital Object Identifier (DOI)
- 10.1016/j.celrep.2016.06.058
Language
- eng
Conference Location
- United States