Mesenchymal stem cell transformation and sarcoma genesis

Abstract

MSCs are hypothesized to potentially give rise to sarcomas after transformation and therefore serve as a good model to study sarcomagenesis. Both spontaneous and induced transformation of MSCs have been reported, however, spontaneous transformation has only been convincingly shown in mouse MSCs while induced transformation has been demonstrated in both mouse and human MSCs. Transformed MSCs of both species can give rise to pleomorphic sarcomas after transplantation into mice, indicating the potential MSC origin of so-called non-translocation induced sarcomas. Comparison of expression profiles and differentiation capacities between MSCs and sarcoma cells further supports this. Deregulation of P53- Retinoblastoma-, PI3K-AKT-and MAPK pathways has been implicated in transformation of MSCs. MSCs have also been indicated as cell of origin in several types of chromosomal translocation associated sarcomas. In mouse models the generated sarcoma type depends on amongst others the tissue origin of the MSCs, the targeted pathways and genes and the differentiation commitment status of MSCs. While some insights are glowing, it is clear that more studies are needed to thoroughly understand the molecular mechanism of sarcomagenesis from MSCs and mechanisms determining the sarcoma type, which will potentially give directions for targeted therapies.

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

“…Since sarcomas have mesenchymal properties, mesenchymal stromal cells (MSCs) have been investigated as the cell of origin. Indeed, driving expression of oncogenes in this cell type can give rise to sarcomas (Mohseny et al, 2009; Rubio et al, 2013; Shimizu et al, 2010; Xiao et al, 2013). However, MSCs are a heterogeneous population of cells.…”

Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition

“…Although mouse MSCs have been consistently clarified to spontaneously undergo tumorigenetic transformation during a long-term expansion in vitro [53,54], the malignant transformation of human MSCs has not been established. Several studies have demonstrated that human MSC were relatively resistant to genomic aberrations and malignant transformation during an in vitro expansion [8,9,11,13,18,[55][56][57][58]. Of interest, Roland et al first reported the spontaneous malignant transformation of human BM-MSCs, with a transformation rate as high as 45.8% (11 of 24) during a long-term (5 --106 weeks) in vitro culture; and the transformed MSCs showed highly tumorigenic ability when they were injected into immunodeficient mice [59].…”

Gingival Leiomyosarcoma in a Young Woman: Case report and literature review

“…8 The most common intraoral site for LMS appears to be the tongue, usually as a result of metastasis from a primary tumour in the uterus, gastrointestinal tract or retroperitoneum. 7,9 Oral LMS may also involve the jaw bones, cheek, gingiva, floor of the mouth, mandible, soft or hard palate and lips. These tumours present with a wide range of clinical features, including painless or painful smooth rubbery firm masses with or without ulceration, tooth mobility, epistaxis, nasal obstruction, otalgia and a variety of other symptoms depending on the site of the lesion.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Besides early diagnosis, the prognosis of oral LMS patients depends on the tumour grade, size, site and treatment. [20][21][22] Currently, there are no standard criteria for therapy, although the complete excision of the tumour with wide surgical margins is recommended.…”