Concise Review: Mesenchymal Tumors: When Stem Cells Go Mad

Abstract

Sarcomas are nonepithelial, nonhematopoietic malignant tumors that arise from the embryonic mesoderm. Despite their rarity, less than 10% of all cancers, sarcomas are accountable for relatively high morbidity and mortality especially in children and adolescents. Although there are some hereditary conditions predisposing sarcoma, such as the LiFraumeni and Retinoblastoma syndrome, the vast majority of these tumors are sporadic. Based on their histological morphology, sarcomas have been divided into a broad spectrum of subtypes recognized in the 2002 WHO classification of tumors. This wide lineage range suggests that sarcomas originate from either many committed different cell types or from a multipotent cell, subsequently driven into a certain lineage. Mesenchymal stem cells (MSCs) are able to differentiate into many cell types needed to create mature structures like vessels, muscle, and bone. These multipotent cells can be isolated from several adult human tissues and massively expanded in culture, making them both of use for research as well as potential beneficial therapeutical agents. For this reason MSCs are being extensively studied, however, concerns have raised about whether they are the putative originating cells of sarcoma and their questionable role in cancer progression. Recent accomplishments in the field have broadened our knowledge of MSCs in relation to sarcoma origin, sarcoma treatment and the safety of MSCs usage in therapeutic settings.

Modeling sarcomagenesis using multipotent mesenchymal stem cells

“…MSCs have been reported to inhibit or promote tumor growth depending on yet undefined conditions [9]. Likewise, the tumoral transformation of MSCs by different mechanisms gives rise to the formation of sarcomas in vivo, hence placing MSCs as the most likely cell of origin for certain sarcomas [10]. Sarcomas comprise a heterogenous group of malignant tumors of mesenchymal origin that were historically grouped according to the tumor location into two main types: soft tissue sarcoma (STS) and primary bone sarcoma [11].…”

Asymmetric Aneuploidy in Mesenchymal Stromal Cells Detected by In Situ Karyotyping and Fluorescence In Situ Hybridization: Suggestions for Reference Values for Stem Cells

“…[7]/46,XY [13] 46,XY,der(7)dup(7)(q32q36)t(7;?)(q36;?) [7]/46,XY [13] a MSCs in which in situ karyotyping analysis was performed for multiple passages. ISCN, International System for Human Cytogenetic Nomenclature.…”

“…However, the clinical use of MSCs is still controversial, due to concerns about their safety [1][2][3]. The most important concern is the tumorigenesis potential of the MSCs [4][5][6][7]. Chromosomal aberration is one of the hallmarks of human cancer, and therefore, it is important to evaluate the chromosomal stability and variability of MSCs before they are used in clinical applications [8].…”

Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter

“…The stem cells are committed to differentiate into chondrocytes and, once acquiring genetic alterations in other genes than EXT1/EXT2 and IDH1/IDH2, originate chondrosarcomas and not other type of bone tumours. It has been proposed that sarcoma in general is a differentiation disease, caused by mutations hampering terminal differentiation of mesenchymal stem cells [80]. Depending on the lineage and the stage of differentiation at the time of the mutation, sarcomas with variable phenotype and histological grade could be initiated [80].…”

“…It has been proposed that sarcoma in general is a differentiation disease, caused by mutations hampering terminal differentiation of mesenchymal stem cells [80]. Depending on the lineage and the stage of differentiation at the time of the mutation, sarcomas with variable phenotype and histological grade could be initiated [80]. Gene expression profiles of differentiated chondrosarcoma (ie low-grade chondrosarcomas) share similarities with fully differentiated chondrocytes (ie growth plate chondrocytes and osteochondroma cells), whereas less differentiated chondrosarcomas (ie high-grade chondrosarcomas) show overlap with pre-chondrogenic stages of mesenchymal stem cells [81].…”