Circulating tumor cells: hope to diagnose and treat metastatic cancer

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

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Abstract 3604: Centrosome amplification in epcam-captured circulating tumor cells from metastatic cancer patients

10.1158/1538-7445.am2018-3604 ◽

2018 ◽

Cited By ~ 1

Author(s):

Ashok Singh ◽

Ryan A. Denu ◽

Jamie M. Sperger ◽

Beth A. Weaver ◽

Mark E. Burkard ◽

...

Keyword(s):

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Cancer ◽

Centrosome Amplification

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Efficient Propagation of Circulating Tumor Cells: A First Step for Probing Tumor Metastasis

Cancers ◽

10.3390/cancers12102784 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2784

Author(s):

Jerry Xiao ◽

Joseph R. McGill ◽

Kelly Stanton ◽

Joshua D. Kassner ◽

Sujata Choudhury ◽

...

Keyword(s):

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Cancer ◽

Metastatic Breast ◽

Success Rates ◽

Breast Cancer Patients ◽

Metastatic Cells ◽

Healthy Donors

Circulating tumor cells (CTCs) represent a unique population of cells that can be used to investigate the mechanistic underpinnings of metastasis. Unfortunately, current technologies designed for the isolation and capture of CTCs are inefficient. Existing literature for in vitro CTC cultures report low (6−20%) success rates. Here, we describe a new method for the isolation and culture of CTCs. Once optimized, we employed the method on 12 individual metastatic breast cancer patients and successfully established CTC cultures from all 12 samples. We demonstrate that cells propagated were of breast and epithelial origin. RNA-sequencing and pathway analysis demonstrated that CTC cultures were distinct from cells obtained from healthy donors. Finally, we observed that CTC cultures that were associated with CD45+ leukocytes demonstrated higher viability. The presence of CD45+ leukocytes significantly enhanced culture survival and suggests a re-evaluation of the methods for CTC isolation and propagation. Routine access to CTCs is a valuable resource for identifying genetic and molecular markers of metastasis, personalizing the treatment of metastatic cancer patients and developing new therapeutics to selectively target metastatic cells.

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Microtube Device for Selectin-Mediated Capture of Viable Circulating Tumor Cells from Blood

Clinical Chemistry ◽

10.1373/clinchem.2011.176669 ◽

2012 ◽

Vol 58 (5) ◽

pp. 846-853 ◽

Cited By ~ 72

Author(s):

Andrew D Hughes ◽

Jeff Mattison ◽

Laura T Western ◽

John D Powderly ◽

Bryan T Greene ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Cancer ◽

Capture Rate ◽

Buffy Coat ◽

Cellular Damage ◽

Cancer Therapies ◽

Microscale Flow ◽

Coated Surface ◽

Personalized Cancer

Abstract BACKGROUND Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage. METHODS We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer. RESULTS Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20–704 viable CTCs per 3.75-mL sample, achieving purities of 18%–80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading. CONCLUSIONS The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.

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Epithelial Mesenchymal Transition: A New Insight into the Detection of Circulating Tumor Cells

ISRN Oncology ◽

10.5402/2012/382010 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 16

Author(s):

Guislaine Barrière ◽

Michel Tartary ◽

Michel Rigaud

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

New Technologies ◽

Epithelial Mesenchymal Transition ◽

Metastatic Cancer ◽

Biological Marker ◽

Molecular Characteristics ◽

Mesenchymal Transition ◽

Patient Will ◽

Worse Prognosis

Many research groups reported on the relation between circulating tumor cells (CTCs) in peripheral blood and worse prognosis for metastatic cancer patients. These results are based on CTCs counting and did not take into account molecular characteristics of cells. To establish CTCs as a reliable and accurate biological marker, new technologies must be focused on CTC subpopulations: dedifferentiated circulating tumor cells (ddCTCs) arising from epithelial mesenchymal transition (EMT). To select and detect them, different methods have been proposed but none has still reached the goal. Technical progress and translational research are expected to establish CTCs as a real marker. Thus CTC evaluation profiling for each patient will lead to personalize followup and therapy.

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Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

Cancer Research ◽

10.1158/0008-5472.can-17-0688 ◽

2017 ◽

Vol 77 (16) ◽

pp. 4530-4541 ◽

Cited By ~ 26

Author(s):

Natali Gulbahce ◽

Mark Jesus M. Magbanua ◽

Robert Chin ◽

Misha R. Agarwal ◽

Xuhao Luo ◽

...

Keyword(s):

Combination Therapy ◽

Whole Genome Sequencing ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Genome Sequencing ◽

Metastatic Cancer ◽

Whole Genome

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Adhesion-based simple capture and recovery of circulating tumor cells using a blood-compatible and thermo-responsive polymer-coated substrate

RSC Advances ◽

10.1039/c6ra15229e ◽

2016 ◽

Vol 6 (92) ◽

pp. 89103-89112 ◽

Cited By ~ 11

Author(s):

Takashi Hoshiba ◽

Toshihiko Orui ◽

Chiho Endo ◽

Kazuhiro Sato ◽

Ayano Yoshihiro ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Biology ◽

Metastatic Cancer ◽

Cancer Diagnostics ◽

Cancer Drug ◽

Coated Substrate ◽

Anti Cancer ◽

Biology Research

Circulating tumor cells (CTCs) have been a focus of study for metastatic cancer diagnostics, in in vitro anti-cancer drug screening to decide the chemotherapeutic course, and cancer biology research.

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Retaining the long-survive capacity of Circulating Tumor Cells (CTCs) followed by xeno-transplantation: not only from metastatic cancer of the breast but also of prostate cancer patients

Oncoscience ◽

10.18632/oncoscience.8 ◽

2013 ◽

Vol 1 (1) ◽

pp. 49-56 ◽

Cited By ~ 29

Author(s):

Elisabetta Rossi ◽

Massimo Rugge ◽

Antonella Facchinetti ◽

Marco Pizzi ◽

Giorgia Nardo ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Cancer

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How Circulating Cancer Cells Disguise: the Role of Platelets

10.21203/rs.3.rs-892511/v1 ◽

2021 ◽

Author(s):

Dorothea Sonja Schott ◽

Monika Pizon ◽

Erika Schill ◽

Katharina Pachmann

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Cancer ◽

Distant Metastases ◽

Blood Collection ◽

Epithelial Tumor ◽

Therapeutic Measures ◽

Epithelial Tumor Cells ◽

Systemic Therapies

Abstract Solid tumors are notorious for their ability to form lethal metastases, sometimes several decades following initial cancer diagnosis. Development of distant metastases is a result of the primary tumor shedding cells that travel via lymphatics and the blood to distant sites where they can form metastases. Platelets are known to specifically enhance tumor cells’ survival in the bloodstream by as yet poorly understood mechanisms. To study the interplay of platelets with circulating tumor cells, we implemented our published approach to label both circulating epithelial tumor cells and platelets. Blood samples were collected avoiding fixation from patients with non-metastatic cancer diagnoses and processed at 4 time points following blood collection. Circulating epithelial tumor cells were undetectable directly after blood collection but became visible after overnight storage at room temperature presumably due to release of platelets from the tumor cells. Our results suggest that platelets play a key role in masking circulating tumor cells. Masking may explain the difficulties in detection of these cells and prevention of their elimination by the immune system. Our unmasking approach detects sufficient numbers of circulating tumor cells to monitor the effect on blood tumor cells of different therapeutic measures, thus contributing to improved systemic therapies for cancer.

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Detection of circulating lymphendothelial cells in patients with solid tumors

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20010 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20010-20010

Author(s):

W. Fiedler ◽

K. Suhrbier ◽

S. Riethdorf ◽

G. Schuch ◽

K. Pantel ◽

...

Keyword(s):

Endothelial Cells ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Healthy Subjects ◽

Metastatic Cancer ◽

Lymphatic Vessels ◽

Lymphatic Endothelial Cells ◽

Tumor Patients

20010 Background: Bone marrow derived endothelial progenitor cells (ECPs) contribute to neoangiogenesis in cancer patients. Elevated numbers of circulating endothelial cells and EPCs can be detected in the peripheral blood of tumor patients. Recently, proliferating lymphatic vessels have been described in human cancers such as melanoma and head and neck tumors. Therefore, we investigated whether circulating lymphatic endothelial cells can be detected in cancer patients. Methods: We developed a sensitive immunocytochemical approach using a monoclonal antibody against the lymphendothelial specific hyaluronic receptor LYVE. After enrichment by Ficoll density gradient centrifugation, 7 × 10(5) peripheral blood mononuclear cells (PBMNCs) from 23 patients with metastatic cancer (6 gastrointestinal, 4 lung, 3 thymus, 3 thyroid, 1 mamma, 1 pancreas, 2 renal, 1 adrenal, 2 urothelial cancer, 1 PNET, 1 NET) and healthy individuals (n = 7) were spun onto glass slides. Two million PBMNs from each patient were stained for LYVE using the APAP technique. Isotype antibodies were used as controls. Cytospins were analyzed with the automated cellular imaging system (ACIS; ChromaVision Medical Systems). The method was validated with spiked blood samples. Results: Circulating LYVE+ lymphatic endothelial cells could be detected in 4 of 7 healthy subjects (57%) and in 16 of 23 patients (69%) with metastatic cancer. The mean number of lymphendothelial cells was significantly higher in cancer patients (15 cells/1 × 10(6) PBMNCs [range 0–276] vs. 1.0 cells/1 × 10(6) PBMNCs [range 0–2]). As a control, circulating tumor cells were enumerated after staining with a cytokeratin antibody (A45-B/B3). Circulating tumor cells could not be detected in healthy controls but in 13 of 23 of cancer patients (mean 1.4 cells/1 × 10(6) PBMNCs range [0–9]). Conclusion: Circulating lymphendothelial cells can be detected in patients with metastatic cancer and healthy subjects. Tumor patients have higher levels of circulating lymphendothelial cells than normal controls. These cells may participate in the generation of lymphatic vessels within tumor manifestations. No significant financial relationships to disclose.

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