Mapping chemotherapeutic drug distribution in cancer cell spheroids using 2D-TOF-SIMS and LESA-TIMS-MS

The Analyst ◽  
2020 ◽  
Vol 145 (21) ◽  
pp. 7056-7062
Author(s):  
Yarixa L. Cintron-Diaz ◽  
Arlet M. Acanda de la Rocha ◽  
Anthony Castellanos ◽  
Jeremy M. Chambers ◽  
Francisco Fernandez-Lima
Keyword(s):  
Cancer Cell ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Drug Distribution ◽  
Chemotherapeutic Drug ◽  
Cell Spheroids ◽  
Tof Sims ◽  
Cancer Tumor ◽  
Effective Models

Three-dimensional (3D) cancer cell cultures grown in the form of spheroids are effective models for the study of in vivo-like processes simulating cancer tumor pharmacological dynamics and morphology.

scholarly journals Organotypic three-dimensional cancer cell cultures mirror drug responses in vivo: lessons learned from the inhibition of EGFR signaling

Oncotarget ◽  
2017 ◽  
Vol 8 (64) ◽  
pp. 107423-107440 ◽  
Author(s):  
Nico Jacobi ◽  
Rita Seeboeck ◽  
Elisabeth Hofmann ◽  
Helmut Schweiger ◽  
Veronika Smolinska ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Lessons Learned ◽  
Egfr Signaling ◽  
Drug Responses

scholarly journals Impedance Study of Dopamine Effects after Application on 2D and 3D Neuroblastoma Cell Cultures Developed on a 3D-Printed Well

Chemosensors ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 6 ◽  
Author(s):  
Georgia Paivana ◽  
Theofylaktos Apostolou ◽  
Sophie Mavrikou ◽  
Dimitris Barmpakos ◽  
Grigoris Kaltsas ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Immobilized Cells ◽  
Neuroblastoma Cell ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Impedance Analysis ◽  
Neural Cells ◽  
Opposite Behavior ◽  
2D And 3D

In this work, the assessment of the interactions of a bioactive substance applied to immobilized cells in either a two-dimensional (2D) or three-dimensional (3D) arrangement mimicking in vivo tissue conditions is presented. In particular, dopamine (DA) was selected as a stimulant for the implementation of an impedance analysis with a specific type of neural cells (murine neuroblastoma). The aim of this study was the extraction of calibration curves at various frequencies with different known dopamine concentrations for the description of the behavior of dopamine applied to 2D and 3D cell cultures. The results present the evaluation of the mean impedance value for each immobilization technique in each frequency. The differential responses showed the importance of the impedance when frequency is applied in both 2D and 3D immobilization cases. More specifically, in 2D immobilization matrix impedance shows higher values in comparison with the 3D cell culture. Additionally, in the 3D case, the impedance decreases with increasing concentration, while in the 2D case, an opposite behavior was observed.

scholarly journals Generation of Homogenous Three-Dimensional Pancreatic Cancer Cell Spheroids Using an Improved Hanging Drop Technique

2016 ◽  
Vol 22 (4) ◽  
pp. 312-321 ◽  
Author(s):  
Matthew J. Ware ◽  
Kevin Colbert ◽  
Vazrik Keshishian ◽  
Jason Ho ◽  
Stuart J. Corr ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Three Dimensional ◽  
Hanging Drop ◽  
Cell Spheroids ◽  
Drop Technique

scholarly journals The Effective Combination between 3D Cancer Models and Stimuli-Responsive Nanoscale Drug Delivery Systems

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3295
Author(s):  
Federica Foglietta ◽  
Loredana Serpe ◽  
Roberto Canaparo
Keyword(s):  
Drug Delivery ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Drug Delivery Systems ◽  
In Vitro Models ◽  
Delivery Systems ◽  
Stimuli Responsive ◽  
Cancer Models

Stimuli-responsive drug-delivery systems (DDSs) have emerged as a potential tool for applications in healthcare, mainly in the treatment of cancer where versatile nanocarriers are co-triggered by endogenous and exogenous stimuli. Two-dimensional (2D) cell cultures are the most important in vitro model used to evaluate the anticancer activity of these stimuli-responsive DDSs due to their easy manipulation and versatility. However, some limitations suggest that these in vitro models poorly predict the outcome of in vivo studies. One of the main drawbacks of 2D cell cultures is their inadequate representation of the 3D environment’s physiological complexity, which sees cells interact with each other and the extracellular matrix (ECM) according to their specific cellular organization. In this regard, 3D cancer models are a promising approach that can overcome the main shortcomings of 2D cancer cell cultures, as these in vitro models possess many peculiarities by which they mimic in vivo tumors, including physiologically relevant cell–cell and cell–ECM interactions. This is, in our opinion, even more relevant when a stimuli-responsive DDS is being investigated. In this review, we therefore report and discuss endogenous and exogenous stimuli-responsive DDSs whose effectiveness has been tested using 3D cancer cell cultures.

scholarly journals The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain

2021 ◽  
Vol 7 (26) ◽  
pp. eabg8139
Author(s):  
Cynthia Hajal ◽  
Yoojin Shin ◽  
Leanne Li ◽  
Jean Carlos Serrano ◽  
Tyler Jacks ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Three Dimensional ◽  
Brain Parenchyma ◽  
Cell Axis ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2 ◽  
The Brain

Although brain metastases are common in cancer patients, little is known about the mechanisms of cancer extravasation across the blood-brain barrier (BBB), a key step in the metastatic cascade that regulates the entry of cancer cells into the brain parenchyma. Here, we show, in a three-dimensional in vitro BBB microvascular model, that astrocytes promote cancer cell transmigration via their secretion of C-C motif chemokine ligand 2 (CCL2). We found that this chemokine, produced primarily by astrocytes, promoted the chemotaxis and chemokinesis of cancer cells via their C-C chemokine receptor type 2 (CCR2), with no notable changes in vascular permeability. These findings were validated in vivo, where CCR2-deficient cancer cells exhibited significantly reduced rates of arrest and transmigration in mouse brain capillaries. Our results reveal that the CCL2-CCR2 astrocyte-cancer cell axis plays a fundamental role in extravasation and, consequently, metastasis to the brain.

Polyacrylamide/GelMA Hydrogel Templates for Breast Cancer Cell Spheroids Fabrication

2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Yuhui Li ◽  
Xiang Li ◽  
Lu Zheng ◽  
Lin Wang ◽  
Xiaohui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Three Dimensional ◽  
Seeding Density ◽  
Cellular Spheroids ◽  
Cell Spheroids ◽  
Functional Tissue ◽  
Regenerative Medicines

Fabrication of cellular spheroids is critical for creating functional tissue units and investigating the mechanism of tumorigenesis, development, and intercellular and cell–matrix interactions in vitro. Herein, we developed a novel, simple, and facile method for cell spheroid fabrication by using polyacrylamide/gelatin methacrylate (PA/GelMA) hydrogel composites. Arrays of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell spheroids can be easily formed by tuning the GelMA composition. The shape and size of cell spheroids can be also well controlled by regulating cell seeding density and culturing time. All these results suggested that this simple and facile platform can serve as a useful tool to generate three-dimensional (3D) cell spheroids and can be integrated within high-throughput drug screening platforms, which will be of great help in engineering functional tissue models and regenerative medicines.

scholarly journals A Novel 3D Scaffold for Cell Growth to Asses Electroporation Efficacy

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1470 ◽  
Author(s):  
Dettin ◽  
Sieni ◽  
Zamuner ◽  
Marino ◽  
Sgarbossa ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Cell Interaction ◽  
Growth Patterns ◽  
3D Scaffold ◽  
Electric Pulses ◽  
Breast Carcinoma Cell Lines ◽  
Cell Cell

Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell–cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell–cell and cell–ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.

scholarly journals Anti-Tumor Effects of Exosomes Derived from Drug-Incubated Permanently Growing Human MSC

2020 ◽  
Vol 21 (19) ◽  
pp. 7311 ◽  
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Large Scale ◽  
Primary Cultures ◽  
Cancer Model ◽  
Oral Gavage ◽  
Cytotoxic Effects ◽  
Breast Cancer Model

Similar to growth-limited human primary cultures of mesenchymal stroma/stem-like cells (MSC), the continuously proliferating human MSC544 cell line produced extracellular vesicles as characterized by expression of the tetraspanin molecules CD9, CD63, and CD81. Release of these particles was predominantly detectable during continuous cell growth of MSC544 in contrast to confluency-mediated transient growth arrest. For therapeutic use, these particles were isolated from proliferating MSC544 after taxol treatment and applied to different cancer cell cultures. A pronounced cytotoxicity of lung, ovarian, and breast cancer cells was observed primarily with taxol-loaded exosomes, similar to the effects displayed by application of taxol substance. While these findings suggested pronounced cancer cell targeting of MSC544 exosomes, a tumor therapeutic approach was performed using a mouse in vivo breast cancer model. Thus, intravenous injection of taxol-loaded MSC544 exosomes displayed superior tumor-reducing capabilities as compared to application of taxol exosomes by oral gavage. To broaden this therapeutic spectrum, epirubicin was applied to MSC544, and the derived exosomes likewise exhibited significant cytotoxic effects in different cancer cell cultures. These findings suggest an unlimited source for large-scale exosome production with reproducible quality to enable variable drug targeting of tumors or other diseases.

scholarly journals Non-Invasive Quantification of the Growth of Cancer Cell Colonies by a Portable Optical Coherence Tomography

Micromachines ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 35 ◽  
Author(s):  
Meng-Tsan Tsai ◽  
Bo-Huei Huang ◽  
Chun-Chih Yeh ◽  
Kin Fong Lei ◽  
Ngan-Ming Tsang
Keyword(s):  
Optical Coherence Tomography ◽  
Cancer Cell ◽  
Cellular Response ◽  
Tumor Development ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Optical Coherence ◽  
Non Invasive

Investigation of tumor development is essential in cancer research. In the laboratory, living cell culture is a standard bio-technology for studying cellular response under tested conditions to predict in vivo cellular response. In particular, the colony formation assay has become a standard experiment for characterizing the tumor development in vitro. However, quantification of the growth of cell colonies under a microscope is difficult because they are suspended in a three-dimensional environment. Thus, optical coherence tomography (OCT) imaging was develop in this study to monitor the growth of cell colonies. Cancer cell line of Huh 7 was used and the cells were applied on a layer of agarose hydrogel, i.e., a non-adherent surface. Then, cell colonies were gradually formed on the surface. The OCT technique was used to scan the cell colonies every day to obtain quantitative data for describing their growth. The results revealed the average volume increased with time due to the formation of cell colonies day-by-day. Additionally, the distribution of cell colony volume was analyzed to show the detailed information of the growth of the cell colonies. In summary, the OCT provides a non-invasive quantification technique for monitoring the growth of the cell colonies. From the OCT images, objective and precise information is obtained for higher prediction of the in vivo tumor development.

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