In Vitro and In Vivo Models of Circulating Tumor Cells

2021 ◽  
pp. 185-195
Author(s):  
Anna Paula Carreta Ruano ◽  
Fernanda Cristina Sulla Lupinacci
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
In Vivo Models

scholarly journals Functional Studies on Viable Circulating Tumor Cells

2016 ◽  
Vol 62 (2) ◽  
pp. 328-334 ◽  
Author(s):  
Klaus Pantel ◽  
Catherine Alix-Panabières
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Diagnostics ◽  
Published Data ◽  
Liquid Biopsies ◽  
In Vivo Models ◽  
Functional Studies

AbstractBACKGROUNDResearch 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.CONTENTThe 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.SUMMARYFunctional 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.

scholarly journals Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish

2021 ◽  
Vol 22 (17) ◽  
pp. 9279
Author(s):  
Inés Martínez-Pena ◽  
Pablo Hurtado ◽  
Nuria Carmona-Ule ◽  
Carmen Abuín ◽  
Ana Belén Dávila-Ibáñez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Molecular Mechanisms ◽  
Zebrafish Embryo ◽  
Cancer Metastasis ◽  
Fluid Shear Stress ◽  
In Vivo Models

Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. Methods: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. Results: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. Conclusions: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.

scholarly journals Molecular and Functional Characterization of Circulating Tumor Cells: From Discovery to Clinical Application

2019 ◽  
Vol 66 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Luis Enrique Cortés-Hernández ◽  
Zahra Eslami-S ◽  
Klaus Pantel ◽  
Catherine Alix-Panabières
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Functional Characterization ◽  
Clinical Information ◽  
In Vivo Models ◽  
Functional Studies

Abstract BACKGROUND One of the objectives for the liquid biopsy is to become a surrogate to tissue biopsies in diagnosis of cancer as a minimally invasive method, with clinical utility in real-time follow-ups of patients. To achieve this goal, it is still necessary to achieve a better understanding of the mechanisms of cancer and the biological principles that govern its behavior, particularly with regard to circulating tumor cells (CTCs). CONTENT The isolation, enumeration, detection, and characterization of CTCs have already proven to provide relevant clinical information about patient prognosis and treatment prediction. Moreover, CTCs can be analyzed at the genome, proteome, transcriptome, and secretome levels and can also be used for functional studies in in vitro and in vivo models. These features, taken together, have made CTCs a very valuable biosource. SUMMARY To further advance the field and discover new clinical applications for CTCs, several studies have been performed to learn more about these cells and better understand the biology of metastasis. In this review, we describe the recent literature on the topic of liquid biopsy with particular focus on the biology of CTCs.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

scholarly journals Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Filled with Carboplatin as a Novel Drug Nanocarrier against Murine Lung Cancer Cells

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1572 ◽  
Author(s):  
Daniel Salas-Treviño ◽  
Odila Saucedo-Cárdenas ◽  
María de Jesús Loera-Arias ◽  
Humberto Rodríguez-Rocha ◽  
Aracely García-García ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Carbon Nanotubes ◽  
Tumor Cells ◽  
Therapeutic Potential ◽  
Cell Uptake ◽  
In Vivo Models ◽  
Multi Wall Carbon Nanotubes ◽  
Lung Cancer Model

Carbon nanotubes (CNTs) have emerged in recent years as a potential option for drug delivery, due to their high functionalization capacity. Biocompatibility and selectivity using tissue-specific biomolecules can optimize the specificity, pharmacokinetics and stability of the drug. In this study, we design, develop and characterize a drug nanovector (oxCNTs-HA-CPT) conjugating oxidated multi-wall carbon nanotubes (oxCNTs) with hyaluronate (HA) and carboplatin (CPT) as a treatment in a lung cancer model in vitro. Subsequently, we exposed TC–1 and NIH/3T3 cell lines to the nanovectors and measured cell uptake, cell viability, and oxidative stress induction. The characterization of oxCNTs-HA-CPT reveals that on their surface, they have HA. On the other hand, oxCNTs-HA-CPT were endocytosed in greater proportion by tumor cells than by fibroblasts, and likewise, the cytotoxic effect was significantly higher in tumor cells. These results show the therapeutic potential that nanovectors possess; however, future studies should be carried out to determine the death pathways involved, as well as their effect on in vivo models.

scholarly journals Breast Tumor Cells Highly Resistant to Drugs Are Controlled Only by the Immune Response Induced in an Immunocompetent Mouse Model

2019 ◽  
Vol 18 ◽  
pp. 153473541984804 ◽  
Author(s):  
Paola Lasso ◽  
Mónica Llano Murcia ◽  
Tito Alejandro Sandoval ◽  
Claudia Urueña ◽  
Alfonso Barreto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
High Capacity ◽  
Cancer Cell Line ◽  
Tumor Model ◽  
Main Element ◽  
In Vivo Models

Background: The tumor cells responsible for metastasis are highly resistant to chemotherapy and have characteristics of stem cells, with a high capacity for self-regeneration and the use of detoxifying mechanisms that participate in drug resistance. In vivo models of highly resistant cells allow us to evaluate the real impact of the immune response in the control of cancer. Materials and Methods: A tumor population derived from the 4T1 breast cancer cell line that was stable in vitro and highly aggressive in vivo was obtained, characterized, and determined to exhibit cancer stem cell (CSC) phenotypes (CD44+, CD24+, ALDH+, Oct4+, Nanog+, Sox2+, and high self-renewal capacity). Orthotopic transplantation of these cells allowed us to evaluate their in vivo susceptibility to chemo and immune responses induced after vaccination. Results: The immune response induced after vaccination with tumor cells treated with doxorubicin decreased the formation of tumors and macrometastasis in this model, which allowed us to confirm the immune response relevance in the control of highly chemotherapy-resistant ALDH+ CSCs in an aggressive tumor model in immunocompetent animals. Conclusions: The antitumor immune response was the main element capable of controlling tumor progression as well as metastasis in a highly chemotherapy-resistant aggressive breast cancer model.

Abstract 1717: Circulating tumor cells from in vitro 3D culture systems have tumor-initiating capacity in vivo

2016 ◽  
Author(s):  
Marina C. Cabrera ◽  
Elaine Hurt ◽  
Xiaoru Chen ◽  
Shi Xiaoqing ◽  
Haifeng Bao
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
3D Culture ◽  
Culture Systems

Tumor cell-platelet interactions in vitro and their relationship to in vivo arrest of hematogenously circulating tumor cells

1987 ◽  
Vol 5 (1) ◽  
pp. 65-78 ◽  
Author(s):  
David G. Menter ◽  
James S. Hatfield ◽  
Carmel Harkins ◽  
Bonnie F. Sloane ◽  
John D. Taylor ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells

scholarly journals Abstract LB-363: Characterization of in vitro and in vivo models generated from disseminated tumor cells of patients without manifest metastasis

2018 ◽  
Author(s):  
Christian Werno ◽  
Kathrin Weidele ◽  
Steffi Treitschke ◽  
Catherine Botteron ◽  
Sebastian Scheitler ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
In Vivo Models

scholarly journals Fluorescence Labeling of Circulating Tumor Cells with Folate Receptor Targeted Molecular Probes for Diffuse In Vivo Flow Cytometry

2020 ◽  
Author(s):  
Roshani Patil ◽  
Madduri Srinivasarao ◽  
Mansoor Amiji ◽  
Philip S. Low ◽  
Mark Niedre
Keyword(s):  
Flow Cytometry ◽  
Animal Models ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Folate Receptor ◽  
Molecular Probes ◽  
Cell Surface Receptor

AbstractPurposeWe recently developed a new instrument called ‘diffuse in vivo flow cytometry’ (DiFC) for enumeration of rare fluorescently-labeled circulating tumor cells (CTCs) in small animals without drawing blood samples. Until now, we have used cell lines that express fluorescent proteins, or were pre-labeled with a fluorescent dye ex-vivo. In this work, we investigated the use of two folate receptor (FR)-targeted fluorescence molecular probes for in vivo labeling of FR+ CTCs for DiFC.MethodsWe used EC-17 and Cy5-PEG-FR fluorescent probes. We studied the affinity of these probes for L1210A and KB cancer cells, both of which over-express FR. We tested the labeling specificity in cells in culture in vitro, in whole blood, and in mice in vivo. We also studied detectability of labeled cells with DiFC.ResultsBoth EC-17 and Cy5-PEG-FR probes had high affinity for FR+ CTCs in cell culture in vitro. However, only EC-17 had sufficient specificity for CTCs in whole blood. EC-17 labeled CTCs were also readily detectable in circulation in mice with DiFC.ConclusionsThis work demonstrates the feasibility of labeling CTCs for DiFC with a cell surface receptor targeted probe, greatly expanding the utility of the method for pre-clinical animal models. Because DiFC uses diffuse light, this method could be also used to enumerate CTCs in larger animal models and potentially even in humans.

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