scholarly journals Nanostructured Surfaces to Target and Kill Circulating Tumor Cells While Repelling Leukocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Michael J. Mitchell ◽  
Carlos A. Castellanos ◽  
Michael R. King
Keyword(s):  
Cell Adhesion ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Halloysite Nanotubes ◽  
Breast Adenocarcinoma ◽  
Hematogenous Metastasis ◽  
Mcf7 Cells ◽  
Nanostructured Surfaces ◽  
Cancer Cell Death

Hematogenous metastasis, the process of cancer cell migration from a primary to distal location via the bloodstream, typically leads to a poor patient prognosis. Selectin proteins hold promise in delivering drug-containing nanocarriers to circulating tumor cells (CTCs) in the bloodstream, due to their rapid, force-dependent binding kinetics. However, it is challenging to deliver such nanocarriers while avoiding toxic effects on healthy blood cells, as many possess ligands that adhesively interact with selectins. Herein, we describe a nanostructured surface to capture flowing cancer cells, while preventing human neutrophil adhesion. Microtube surfaces with immobilized halloysite nanotubes (HNTs) and E-selectin functionalized liposomal doxorubicin (ES-PEG L-DXR) significantly increased the number of breast adenocarcinoma MCF7 cells captured from flow, yet also significantly reduced the number of captured neutrophils. Neutrophils firmly adhered and projected pseudopods on surfaces coated only with liposomes, while neutrophils adherent to HNT-liposome surfaces maintained a round morphology. Perfusion of both MCF7 cells and neutrophils resulted in primarily cancer cell adhesion to the HNT-liposome surface, and induced significant cancer cell death. This work demonstrates that nanostructured surfaces consisting of HNTs and ES-PEG L-DXR can increase CTC recruitment for chemotherapeutic delivery, while also preventing healthy cell adhesion and uptake of therapeutic intended for CTCs.

MDA-MB-231 and HeLa cells attachment to nanostructured zein surfaces

2018 ◽  
Vol 33 (4) ◽  
pp. 361-370
Author(s):  
Hemiao Cui ◽  
Ying Qin ◽  
Gang L Liu ◽  
Graciela W Padua
Keyword(s):  
Cell Adhesion ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Hela Cells ◽  
Tissue Transglutaminase ◽  
Cell Immobilization ◽  
Supporting Evidence ◽  
Surface Attachment ◽  
Nanostructured Surfaces ◽  
Corn Protein

Detection and characterization of tumor cells are important for cancer diagnosis and therapy. Various surface attachment methods have been proposed for the capture and enumeration of cancer cells, including immunoaffinity and nanostructured surfaces. Zein, a corn protein, has shown good biocompatibility with human liver cells (HL-7702) and mice fibroblasts (NIH3T3). In previous work, it was found that tissue transglutaminase coated on zein substrates enhanced adhesion and spreading of NIH3T3 fibroblast cells. In the present study, cancer cell adhesion to nanostructured zein substrates was investigated. MDA-MB-231 and HeLa cells were used as cancer cell surrogates. MDA-MB-231 cell immobilization was enhanced on zein films, prepared with 80% ethanol, over glass surfaces. The application of tissue transglutaminase onto nanostructured zein substrates further increased cell spreading and adhesion. Cell immobilization increased linearly with the tissue transglutaminase content of the substrate. The effect of substrate morphology was also investigated by seeding cells on electrospun zein fibers. HeLa cell adhesion was also enhanced by zein substrates. This study provided preliminary supporting evidence for developing a zein platform for circulating tumor cells’ immobilization.

scholarly journals Mitotic arrest affects clustering of tumor cells

2021 ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaelle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Chemotherapeutic Agents ◽  
The Impact ◽  
Mcf 7

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling

2019 ◽  
Vol 27 (5) ◽  
pp. 1569-1587 ◽  
Author(s):  
Jing Zhang ◽  
Yu Yang ◽  
Shen’ao Zhou ◽  
Xueyan He ◽  
Xuan Cao ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Tumor Regression ◽  
Cell Types ◽  
Tight Contact ◽  
Cancer Cell Death ◽  
Microtubule Targeting Agents ◽  
Patient Responsiveness ◽  
Smac Mimetics

Abstract Microtubule-targeting agents (MTAs) are a class of most widely used chemotherapeutics and their mechanism of action has long been assumed to be mitotic arrest of rapidly dividing tumor cells. In contrast to such notion, here we show—in many cancer cell types—MTAs function by triggering membrane TNF (memTNF)-mediated cancer-cell-to-cancer-cell killing, which differs greatly from other non-MTA cell-cycle-arresting agents. The killing is through programmed cell death (PCD), either in way of necroptosis when RIP3 kinase is expressed, or of apoptosis in its absence. Mechanistically, MTAs induce memTNF transcription via the JNK-cJun signaling pathway. With respect to chemotherapy regimens, our results establish that memTNF-mediated killing is significantly augmented by IAP antagonists (Smac mimetics) in a broad spectrum of cancer types, and with their effects most prominently manifested in patient-derived xenograft (PDX) models in which cell–cell contacts are highly reminiscent of human tumors. Therefore, our finding indicates that memTNF can serve as a marker for patient responsiveness, and Smac mimetics will be effective adjuvants for MTA chemotherapeutics. The present study reframes our fundamental biochemical understanding of how MTAs take advantage of the natural tight contact of tumor cells and utilize memTNF-mediated death signaling to induce the entire tumor regression.

scholarly journals Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepatocellular Circulating Tumor Cells Enrichment

Theranostics ◽  
2016 ◽  
Vol 6 (11) ◽  
pp. 1877-1886 ◽  
Author(s):  
Shuyi Wang ◽  
Chunxiao Zhang ◽  
Guozhou Wang ◽  
Boran Cheng ◽  
Yulei Wang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Nanostructured Surfaces

scholarly journals RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Anja van de Stolpe ◽  
Wim Verhaegh ◽  
Jean-Yves Blay ◽  
Cynthia X. Ma ◽  
Patrick Pauwels ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Target Genes ◽  
Targeted Treatment ◽  
Precision Oncology ◽  
Sequencing Analysis ◽  
Pathway Activity

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples. In contrast, the transcriptome contains information on signaling pathway activity and can complement genomic analyses. Here we present the validation and clinical application of a new knowledge-based mRNA-based diagnostic assay platform (OncoSignal) for measuring activity of relevant signaling pathways simultaneously and quantitatively with high resolution in tissue samples and circulating tumor cells, specifically with very small specimen quantities. The approach uses mRNA levels of a pathway’s direct target genes, selected based on literature for multiple proof points, and used as evidence that a pathway is functionally activated. Using these validated target genes, a Bayesian network model has been built and calibrated on mRNA measurements of samples with known pathway status, which is used next to calculate a pathway activity score on individual test samples. Translation to RT-qPCR assays enables broad clinical diagnostic applications, including small analytes. A large number of cancer samples have been analyzed across a variety of cancer histologies and benchmarked across normal controls. Assays have been used to characterize cell types in the cancer cell microenvironment, including immune cells in which activated and immunotolerant states can be distinguished. Results support the expectation that the assays provide information on cancer driving signaling pathways which is difficult to derive from next generation DNA sequencing analysis. Current clinical oncology applications have been complementary to genomic mutation analysis to improve precision medicine: (1) prediction of response and resistance to various therapies, especially targeted therapy and immunotherapy; (2) assessment and monitoring of therapy efficacy; (3) prediction of invasive cancer cell behavior and prognosis; (4) measurement of circulating tumor cells. Preclinical oncology applications lie in a better understanding of cancer behavior across cancer types, and in development of a pathophysiology-based cancer classification for development of novel therapies and precision medicine.

scholarly journals Cold Physical Plasma in Cancer Therapy: Mechanisms, Signaling, and Immunity

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Fatemeh Faramarzi ◽  
Parisa Zafari ◽  
Mina Alimohammadi ◽  
Mohammadreza Moonesi ◽  
Alireza Rafiei ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Plasma Treatment ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Intracellular Signaling ◽  
Current Knowledge ◽  
Cancer Cell Death ◽  
Physical Plasma

Despite recent advances in therapy, cancer still is a devastating and life-threatening disease, motivating novel research lines in oncology. Cold physical plasma, a partially ionized gas, is a new modality in cancer research. Physical plasma produces various physicochemical factors, primarily reactive oxygen and nitrogen species (ROS/RNS), causing cancer cell death when supplied at supraphysiological concentrations. This review outlines the biomedical consequences of plasma treatment in experimental cancer therapy, including cell death modalities. It also summarizes current knowledge on intracellular signaling pathways triggered by plasma treatment to induce cancer cell death. Besides the inactivation of tumor cells, an equally important aspect is the inflammatory context in which cell death occurs to suppress or promote the responses of immune cells. This is mainly governed by the release of damage-associated molecular patterns (DAMPs) to provoke immunogenic cancer cell death (ICD) that, in turn, activates cells of the innate immune system to promote adaptive antitumor immunity. The pivotal role of the immune system in cancer treatment, in general, is highlighted by many clinical trials and success stories on using checkpoint immunotherapy. Hence, the potential of plasma treatment to induce ICD in tumor cells to promote immunity targeting cancer lesions systemically is also discussed.

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