scholarly journals A universal tumor cell isolation method enabled by fibrin-coated microchannels

The Analyst ◽  
2016 ◽  
Vol 141 (2) ◽  
pp. 563-566 ◽  
Author(s):  
Jinling Zhang ◽  
Z. Hugh Fan
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Isolation ◽  
Mesenchymal Tumor ◽  
Isolation Method

We found that the fibrin-immobilized surfaces on microchannels were able to capture both epithelial and mesenchymal tumor cells.

scholarly journals Targeting CDK4 overcomes EMT-mediated tumor heterogeneity and therapeutic resistance in KRAS mutant lung cancer

2021 ◽  
Author(s):  
Aparna Padhye ◽  
Jessica Konen ◽  
B. Leticia Rodriguez ◽  
Jared Fradette ◽  
Joshua Ochieng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Single Agent ◽  
Mesenchymal Tumor ◽  
Intratumor Heterogeneity ◽  
In Vivo Models ◽  
Mek Inhibitors ◽  
Mesenchymal Transition

Abstract Lack of sustained response to therapeutic agents in patients with K-Ras mutant lung cancer poses a major challenge and arises partly due to intratumor heterogeneity that defines phenotypically distinct tumor subpopulations. To attain better therapeutic outcomes it is important to understand the differential therapeutic sensitivities of tumor cell subsets. Epithelial-to-mesenchymal transition (EMT) is a biologic phenomenon that can alter the phenotypic state and cause transcriptional rewiring to produce distinct tumor cell populations. We utilized functional shRNA screens, in vitro and in vivo models to identify and confirm an increased dependence of mesenchymal tumor cells on CDK4 for survival, as well as a mechanism of resistance to MEK inhibitors. High ZEB1 levels in mesenchymal tumor cells repressed p21, leading to perturbed CDK4 pathway activity. Increased dependence on CDK4 rendered mesenchymal cancer cells particularly vulnerable to selective CDK4 inhibitors. Co-administration of CDK4 and MEK inhibitors in heterogeneous tumors effectively targeted different tumor subpopulations, subverting the resistance to either single agent treatment.

Isolation of Circulating Tumor Cells Using Stiffness-Based Filtration Platform

2015 ◽  
Author(s):  
Emrah Celik ◽  
Nicolas Rongione ◽  
Amelia Bahamonde ◽  
Zheng Ao ◽  
Ram Datar
Keyword(s):  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Blood Cells ◽  
High Efficiency ◽  
White Blood Cells ◽  
Cell Isolation ◽  
Element Analysis ◽  
Cancer Disease

Analysis of isolated cancer cells in circulation is proven to help determine the success of the cancer treatment and understand the genetic signature of cancer disease. Scarcity of these cells in blood circulation (1–10 CTC in 1ml blood) however, makes the isolation process extremely challenging. Ever improving CTC isolation methods fall into two main categories: 1.Immunomagnetic separation based on antibody binding to tumor specific biomarkers expressed on the cell 2. Physical separation based on the size of the CTCs. Efficiency in cell isolation is still low in these techniques due to the variation in expression level of tumor specific antigens and tumor cell size. Therefore, tumor cell isolation strategies using new CTC biomarkers must be explored. In this study, we investigated the feasibility of using mechanical stiffness difference in order to detect and isolate the circulating tumor cells from the blood cells. AFM nanindentation experiments revealed that cancer cells are significantly softer than the surrounding white blood cells and therefore, stiffness can be used as a biomarker for CTC isolation. In addition, finite element analysis simulations have shown that CTC isolation can be performed at high efficiency using stiffness-based isolation. Therefore, stiffness based isolation has a potential to achieve fast, label-free isolation of CTCs at high efficiency for clinical applications.

scholarly journals Evaluation of a marker independent isolation method for circulating tumor cells in esophageal adenocarcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251052
Author(s):  
Annouck Philippron ◽  
Lieven Depypere ◽  
Steffi Oeyen ◽  
Bram De Laere ◽  
Charlotte Vandeputte ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Esophageal Adenocarcinoma ◽  
Healthy Donor ◽  
Positive Staining ◽  
Isolation Method ◽  
Donor Blood ◽  
Tumor Stages

Objective The enrichment of circulating tumor cells (CTCs) from blood provides a minimally invasive method for biomarker discovery in cancer. Longitudinal interrogation allows monitoring or prediction of therapy response, detection of minimal residual disease or progression, and determination of prognosis. Despite inherent phenotypic heterogeneity and differences in cell surface marker expression, most CTC isolation technologies typically use positive selection. This necessitates the optimization of marker-independent CTC methods, enabling the capture of heterogenous CTCs. The aim of this report is to compare a size-dependent and a marker-dependent CTC-isolation method, using spiked esophageal cells in healthy donor blood and blood from patients diagnosed with esophageal adenocarcinoma. Methods Using esophageal cancer cell lines (OE19 and OE33) spiked into blood of a healthy donor, we investigated tumor cell isolation by Parsortix post cell fixation, immunostaining and transfer to a glass slide, and benchmarked its performance against the CellSearch system. Additionally, we performed DEPArray cell sorting to infer the feasibility to select and isolate cells of interest, aiming towards downstream single-cell molecular characterization in future studies. Finally, we measured CTC prevalence by Parsortix in venous blood samples from patients with various esophageal adenocarcinoma tumor stages. Results OE19 and OE33 cells were spiked in healthy donor blood and subsequently processed using CellSearch (n = 16) or Parsortix (n = 16). Upon tumor cell enrichment and enumeration, the recovery rate ranged from 76.3 ± 23.2% to 21.3 ± 9.2% for CellSearch and Parsortix, respectively. Parsortix-enriched and stained cell fractions were successfully transferred to the DEPArray instrument with preservation of cell morphology, allowing isolation of cells of interest. Finally, despite low CTC prevalence and abundance, Parsortix detected traditional CTCs (i.e. cytokeratin+/CD45-) in 8/29 (27.6%) of patients with esophageal adenocarcinoma, of whom 50% had early stage (I-II) disease. Conclusions We refined an epitope-independent isolation workflow to study CTCs in patients with esophageal adenocarcinoma. CTC recovery using Parsortix was substantially lower compared to CellSearch when focusing on the traditional CTC phenotype with CD45-negative and cytokeratin-positive staining characteristics. Future research could determine if this method allows downstream molecular interrogation of CTCs to infer new prognostic and predictive biomarkers on a single-cell level.

Microfluidic technologies for circulating tumor cell isolation

The Analyst ◽  
2018 ◽  
Vol 143 (13) ◽  
pp. 2936-2970 ◽  
Author(s):  
Hyungseok Cho ◽  
Jinho Kim ◽  
Hanjung Song ◽  
Keun Yong Sohn ◽  
MinHyon Jeon ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Circulatory System ◽  
Circulating Tumor Cell ◽  
Cell Isolation ◽  
Critical Step ◽  
Metastatic Process ◽  
Tumor Related Death

Metastasis is the main cause of tumor-related death, and the dispersal of tumor cells through the circulatory system is a critical step in the metastatic process.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

scholarly journals Clusters, Assemblies and Aggregates of Tumor Cells in the Blood of Breast Cancer Patients; Composition, Mode of Action, Detection and Impact on Metastasis and Survival

2021 ◽  
Vol 1 (1) ◽  
pp. 55-68
Author(s):  
Urszula Smietanka ◽  
Małgorzata Szostakowska-Rodzos ◽  
Sylwia Tabor ◽  
Anna Fabisiewicz ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Diagnostic Tool ◽  
Therapeutic Target ◽  
Mode Of Action ◽  
Breast Cancer Patients ◽  
Single Ctcs ◽  
Methods Of Isolation

Circulating tumor cells (CTCs) are gaining momentum as a diagnostic tool and therapeutic target. CTC clusters are more metastatic, but harder to study and characterize, because they are rare and the methods of isolation are mostly focused on single CTCs. This review highlights the recent advances to our understanding of tumor cell clusters with the emphasis on their composition, origin, biology, methods of detection, and impact on metastasis and survival. New approaches to therapy, based on cluster characteristics are also described.

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