Prognostic Relevance of Viable Circulating Tumor Cells Detected by EPISPOT in Metastatic Breast Cancer Patients

Ramírez, J. L. Vega; Fehm, Tanja; Orsini, Mattéa; Cayrefourcq, Laure; Maudelondé, Thierry; Pantel, Klaus; Alix‐Panabières, Catherine

doi:10.1373/clinchem.2013.215079

Cited by 105 publications

(68 citation statements)

References 24 publications

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“…Short-term cultures of CTCs have become possible by the EPISPOT assay 10 years ago (9); this assay detects specific proteins secreted during the in vitro culture of CTCs (10), and clinical studies in breast and colon cancer indicate that the detection of viable CTCs is associated with an unfavorable outcome (11,12). First ex vivo expansion of CTCs has been described in breast cancer by Zhang and colleagues (13) and more recently by Yu and colleagues (14).…”

Section: Introductionmentioning

confidence: 99%

Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells

et al. 2015

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Circulating tumor cells (CTC) in blood are promising new biomarkers potentially useful for prognostic prediction and monitoring of therapies in patients with solid tumors including colon cancer. Moreover, CTC research opens a new avenue for understanding the biology of metastasis in patients with cancer. However, an in-depth investigation of CTCs is hampered by the very low number of these cells, especially in the blood of patients with colorectal cancer. Thus, the establishment of cell cultures and permanent cell lines from CTCs has become the most challenging task over the past year. Here, we describe, for the first time, the establishment of cell cultures and a permanent cell line from CTCs of one patient with colon cancer. The cell line designated CTC-MCC-41 has been cultured for more than one year, and the cells Ó2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells

et al. 2015

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“…A similar approach (CD45 depletion) is used in the so-called EPISPOT assay [10,11]. However, this assay requires technically challenging detection and nonstandard equipment for subsequent detection.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Utility of Unbiased Circulating Tumour Cell Capture through Negative Depletion of Peripheral Blood Cells

et al. 2015

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Objectives: Cytological analysis of peripheral blood circulating tumour cells (CTCs) is a potential method of confirmatory clinical diagnosis of cancer. However, cell capture methods tend to be biased and captured cells are not usually portable resulting in difficulties in pathology reporting. We evaluated unbiased cell capture through depletion of unwanted normal cells and conventional clinical analyses of captured cells. Methods: Blood was sampled from 29 patients who underwent surgery for suspected lung cancer. It was processed using two different depletion cocktails. After depletion of unwanted cells, the resultant cell pellet was processed onto glass slides or embedded into FFPE blocks and stained using standard haematoxylin and eosin staining followed by cytopathologic assessment. Two pathologists performed the assessment independently. Results: The CTCs were identified in 38-45% of cases using CD45 depletion cocktail with the cell pellet processed on a glass slide, while other combinations of methods produced poorer results. Overall, there was a good concordance between the pathologists (up to 91.3%). The sensitivity of cancer diagnosis was 42% (95% CI 23-63%), while the specificity was 100% (95% CI 29-100%). Conclusion: Negative depletion can be used to isolate CTCs in standard clinical settings; however, more effective ways of detection are required to increase the sensitivity of the diagnosis.

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“…To our knowledge, the only existing functional test that has been used on hundreds of patients with different tumor types is EPISPOT, which allows the detection of viable clinically relevant CTCs enriched by leukocyte depletion (23,24 ). This technology enables the detection of EpCAM ϩ and EpCAM Ϫ CTCs.…”

Section: Detection Of Viable Ctcsmentioning

confidence: 99%

“…Cells are cultured for a short time on a membrane coated with antibodies that capture the secreted/released/shed tumorassociated proteins, which are subsequently detected by secondary antibodies labeled with fluorochromes. For breast cancer, cytokeratin 19 (CK19), HER2, cathepsin D, and MUC-1 have been used as marker proteins, and the associated clinical data have shown that patients with CK19-releasing cells had an unfavorable outcome (24,25 ). For prostate cancer, prostate-specific antigen has been used for CTC detection and fibroblast growth factor 2 as stem cell growth factor for further characterization (26 ).…”

Section: Detection Of Viable Ctcsmentioning

confidence: 99%

Functional Studies on Viable Circulating Tumor Cells

Pantel

Alix‐Panabières

2016

Clinical Chemistry

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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.

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Prognostic Relevance of Viable Circulating Tumor Cells Detected by EPISPOT in Metastatic Breast Cancer Patients

Cited by 105 publications

References 24 publications

Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells

Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells

Diagnostic Utility of Unbiased Circulating Tumour Cell Capture through Negative Depletion of Peripheral Blood Cells

Functional Studies on Viable Circulating Tumor Cells

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