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

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

Author information

1
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Department of Orthopaedic Surgery, Tokyo Medical and Dental, University Graduate School and Faculty of Medicine, Tokyo 113-8510, Japan; Department of Physiology and Cell Biology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
2
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Department of Orthopaedic Surgery, Duke University, Durham, NC 27710, USA.
3
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
4
Department of Orthopaedic Surgery, Seoul National University Hospital, Seoul 151-742, Republic of Korea.
5
Department of Orthopaedic Surgery, Tokyo Medical and Dental, University Graduate School and Faculty of Medicine, Tokyo 113-8510, Japan.
6
Department of Physiology and Cell Biology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
7
Department of Orthopaedic Surgery, Duke University, Durham, NC 27710, USA.
8
Department of Radiation Oncology, Duke University, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
9
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
10
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Department of Orthopaedic Surgery, Duke University, Durham, NC 27710, USA. Electronic address: ben.alman@duke.edu.

Abstract

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.

PMID:
27425618
PMCID:
PMC4963269
DOI:
10.1016/j.celrep.2016.06.058
[Indexed for MEDLINE]
Free PMC Article

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