Klaus Pantel1, Catherine Alix-Panabières2. 1. Department of Tumor Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 2. Laboratory of Rare Human Circulating Cells, Department of Cellular and Tissue Biopathology of Tumors, University Medical Centre, Montpellier, France; EA2415-Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research, Montpellier University, Montpellier, France. c-panabieres@chu-montpellier.fr.
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.
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 cancerpatients 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 cancerpatients 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.
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