Functional Studies on Viable Circulating Tumor Cells

Abstract

BACKGROUND Research on circulating tumor cells (CTCs) as new biomarkers has received great attention over the past decade. In particular, the capture and analysis of CTCs as “liquid biopsies” provides the possibility to avoid invasive tissue biopsies, with obvious implications in cancer diagnostics. CONTENT The focus of this review is to describe and discuss how functional studies on viable CTCs can enlarge the spectrum of applications of liquid biopsies, with emphasis on breast, prostate, colon, and lung cancer as the major tumor entities in industrialized countries. The low number of CTCs in the peripheral blood of most cancer patients makes challenging the in vitro culture of CTCs. Epithelial tumor cells are difficult to culture, even when starting with millions of tumor cells. Recently, several groups have achieved important advances in the in vitro and in vivo expansion of CTCs from cancer patients at very advanced stages with higher amounts of CTCs. Here, we present current technologies to enrich and detect viable human CTCs, including positive and negative enrichment strategies that are based on antigen expression and physical properties of CTCs. We also discuss published data about functional studies on CTCs that use in vitro and in vivo models. SUMMARY Functional analyses on CTCs offer the possibility to identify the biological properties of metastatic cells, including the identification of metastasis-initiating cells. Moreover, CTC-derived cell lines and xenografts might reveal new therapeutic targets and can be used for drug screening.

Circulating Tumor Cells as a Biomarker in Pancreatic Ductal Adenocarcinoma

“…They have been demonstrated to open a new research field in diagnosing, evaluating clinical effect, and monitoring recurrence in ovarian cancer [15]. Functional analysis of CTCs based on in vitro and in vivo models from breast, prostate and colon cancers have also attracted some interest due to the possibility of revealing the biological properties of metastatic cells [16]. The epithelial and mesenchymal markers of CTCs have been reported to change with disease progression in breast cancer [17].…”

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

“…CTCs can then be detected using immunologic, molecular, or functional assays ( 15 ). In the past, many research teams focused on functional tests using CTC cultures/cell lines and xenografts ( 29,30 ). These in vitro and in vivo models can be used to test drug susceptibility.…”

Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring

“…CTCs enrichment is either based on biological or physical properties (18). Biological properties include those approaches targeting epithelial specific surface markers like epithelial cell adhesion molecule (EpCAM) for positive selection (e.g., CellSearch TM , microfluidic devices or the nanodetector) or CD45 for negative depletion (19,20 (21). The development of a unique microfluidic platform, the "CTCs-chip", has been demonstrated to be capable of efficient and selective separation of viable CTCs from peripheral whole blood samples.…”