Soft Tissue Sarcoma Cancer Stem Cells: An Overview

Abstract

Soft tissue sarcomas (STSs) are an uncommon group of solid tumors that can arise throughout the human lifespan. Despite their commonality as non-bony cancers that develop from mesenchymal cell precursors, they are heterogeneous in their genetic profiles, histology, and clinical features. This has made it difficult to identify a single target or therapy specific to STSs. And while there is no one cell of origin ascribed to all STSs, the cancer stem cell (CSC) principle—that a subpopulation of tumor cells possesses stem cell-like properties underlying tumor initiation, therapeutic resistance, disease recurrence, and metastasis—predicts that ultimately it should be possible to identify a feature common to all STSs that could function as a therapeutic Achilles' heel. Here we review the published evidence for CSCs in each of the most common STSs, then focus on the methods used to study CSCs, the developmental signaling pathways usurped by CSCs, and the epigenetic alterations critical for CSC identity that may be useful for further study of STS biology. We conclude with discussion of some challenges to the field and future directions.

Sarcoma treatment in the era of molecular medicine

“…Common methods of isolating/enriching CSCs to model sarcoma heterogeneity in vitro include culturing floating three‐dimensional (3D)‐colonies (tumorspheres), cell sorting based on the expression of specific markers (i.e., CD133, ABCG2, CD44, CD184, STRO1, CD117, CD271, or aldehyde dehydrogenase 1), the ability to extrude fluorescent dyes (side populations), or the selective pressure induced by long‐term culturing with chemotherapeutic drugs. CSCs have been extensively characterized in both bone sarcomas and STSs (Salerno et al , 2013; Abarrategi et al , 2016; Brown et al , 2018; Genadry et al , 2018; Skoda & Veselska, 2018; Hatina et al , 2019; Schiavone et al , 2019; Fig 2).…”

Global computational alignment of tumor and cell line transcriptional profiles

“…5e, f), reflecting a stronger mesenchymal expression pattern among these undifferentiated cell lines. The few tumor samples in this cluster were primarily from cancer types with mesenchymal cell lineages 47 and GSEA of genes differentially expressed by these samples showed elevated expression of the EMT pathway (normalized enrichment score = 3.33, adjusted p-value = 6.2e-05).…”

SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications

“…Subpopulations expressing these pluripotency factors have been correlated with tumor progression, drug resistance and the presence of hierarchically organized CSCs in several types of tumors [3][4][5][6][7][8]. In sarcomas, SOX2 has been found overexpressed in CSCs from different subtypes [9][10][11][12][13][14][15][16][17][18] and was described to play specific pro-tumorigenic roles in osteosarcoma [19][20][21]. In addition, OCT-4 expression was also associated to CSCs subpopulations in Ewing sarcoma and osteosarcoma [22,23].…”