The Challenges of Detecting Circulating Tumor Cells in Sarcoma

Abstract

Sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin, many of which have a propensity to develop distant metastases. Cancer cells that have escaped from the primary tumor are able to invade into surrounding tissues, to intravasate into the bloodstream to become circulating tumor cells (CTCs), and are responsible for the generation of distant metastases. Due to the rarity of these tumors and the absence of specific markers expressed by sarcoma tumor cells, the characterization of sarcoma CTCs has to date been relatively limited. Current techniques for isolating sarcoma CTCs are based on size criteria, the identification of circulating cells that express either common mesenchymal markers, sarcoma-specific markers, such as CD99, CD81, or PAX3, and chromosomal translocations found in certain sarcoma subtypes, such as EWS-FLI1 in Ewing's sarcoma, detection of osteoblast-related genes, or measurement of the activity of specific metabolic enzymes. Further studies are needed to improve the isolation and characterization of sarcoma CTCs, to demonstrate their clinical significance as predictive and/or prognostic biomarkers, and to utilize CTCs as a tool for investigating the metastatic process in sarcoma and to identify novel therapeutic targets. The present review provides a short overview of the most recent literature on CTCs in sarcoma.

Keywords: cancer stem cells; circulating tumor cells; neuroblastoma; rare cancers; sarcoma.

Figure 1

The metastatic process in sarcoma and possible fates of cancer cells in secondary site. (A) Cells escaping from the primary tumor into the blood circulation (1) are carried by the flow, either blood stream or lymphatic system (2), to secondary sites where they grow if they find a favorable environment (3). (B) Following the arrival of CTCs into a secondary organ, only a subset will survive and generate metastases (clinically detectable) and remainder cells might either go into a state of dormancy/quiescence or die (clinically undetectable).