scholarly journals A mechanobiological model for tumor spheroids evolution: application to glioblastoma

2021 ◽  
Author(s):  
Ana Carrasco-Mantis ◽  
Hector Castro-Abril ◽  
Teodora Randelovic ◽  
Ignacio Ochoa ◽  
Manuel Doblare ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Formation ◽  
Cellular Growth ◽  
Initial Configuration ◽  
Mechanical Activity ◽  
Model Parameters ◽  
Tumor Spheroids ◽  
Cancer Disease ◽  
Hydrogel Matrix

Spheroids are in vitro spherical structures of cell aggregates, eventually cultured within a hydrogel matrix, that are used, among other applications, as a technological platform to investigate tumor formation and evolution. Several interesting features can be replicated using this methodology, such as cell communication mechanisms, the effect of gradients of nutrients, or the creation of realistic 3D biological structures. In this paper, we propose a continuum mechanobiological model which accounts for the most relevant phenomena that take place in tumor spheroids evolution under in vitro suspension, namely, nutrients diffusion in the spheroid, kinetics of cellular growth and death, and mechanical interactions among the cells. The model is qualitatively validated, after calibration of the model parameters, versus in vitro experiments of spheroids of different glioblastoma cell lines. This preliminary validation allowed us to conclude that glioblastoma tumor spheroids evolution is mainly driven by mechanical interactions of the cell aggregate and the dynamical evolution of the cell population. In particular, it is concluded that our model is able to explain quite different setups, such as spheroids growth (up to six times the initial configuration for U-87 MG cell line) or shrinking (almost half of the initial configuration for U-251 MG cell line); as the result of the mechanical interplay of cells driven by cellular evolution. Indeed, the main contribution of this work is to link the spheroid evolution with the mechanical activity of cells, coupled with nutrient consumption and the subsequent cell dynamics. All this information can be used to further investigate mechanistic effects in the evolution of tumors and their role in cancer disease.

New Platinum (II) Ternary Complexes of Formamidine and Pyrophosphate: Synthesis, Characterization and DFT Calculations and In vitro Cytotoxicity

2020 ◽  
Vol 23 (7) ◽  
pp. 611-623
Author(s):  
Ahmed A. Soliman ◽  
Fawzy A. Attaby ◽  
Othman I. Alajrawy ◽  
Azza A.A. Abou-hussein ◽  
Wolfgang Linert
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Theoretical Calculations ◽  
Thermal Analyses ◽  
Cancer Cell Line ◽  
Cellular Growth ◽  
Planar Geometry ◽  
Square Planar ◽  
Vis Spectroscopy

Aim and Objective: Platinum (II) and platinum (IV) of pyrophosphate complexes have been prepared and characterized to discover their potential as antitumor drugs. This study was conducted to prepare and characterize new ternary platinum (II) complexes with formamidine and pyrophosphate as an antitumor candidate. Materials and Methods: The complexes have been characterized by mass, infrared, UV-Vis. spectroscopy, elemental analysis, magnetic susceptibility, thermal analyses, and theoretical calculations. They have been tested for their cytotoxicity, which was carried out using the fastcolorimetric assay for cellular growth and survival against MCF-7 (breast cancer cell line), HCT- 116 (colon carcinoma cell line), and HepG-2 (hepatocellular cancer cell line). Results: All complexes are diamagnetic, and the electronic spectral data displayed the bands due to square planar Pt(II) complexes. The optimized complexes structures (1-4) indicated a distorted square planar geometry where O-Pt-O and N-Pt-N bond angles were 82.04°-96.44°, respectively. Conclusion: The complexes showed noticeable cytotoxicity and are considered as promising antitumor candidates for further applications.

Interactions Between Bladder Tumor Cells as Tumor Spheroids from the Cell Line J82 and Human Endothelial Cells in Vitro

1988 ◽  
Vol 139 (3) ◽  
pp. 640-645 ◽  
Author(s):  
Ruth Knüchel ◽  
J. Feichtinger ◽  
A. Recktenwald ◽  
H.G. Hollweg ◽  
P. Franke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Line ◽  
Tumor Cells ◽  
Bladder Tumor ◽  
Human Endothelial Cells ◽  
Tumor Spheroids

scholarly journals RUNX3 Promotes the Tumorigenic Phenotype in KGN, a Human Granulosa Cell Tumor-Derived Cell Line

2019 ◽  
Vol 20 (14) ◽  
pp. 3471 ◽  
Author(s):  
Huachen Chen ◽  
Powel Crosley ◽  
Abul K. Azad ◽  
Nidhi Gupta ◽  
Nisha Gokul ◽  
...  
Keyword(s):  
Cell Line ◽  
Granulosa Cell ◽  
Cell Lines ◽  
Granulosa Cell Tumor ◽  
Tumor Formation ◽  
Dominant Negative ◽  
Cell Cycle Regulators ◽  
Cyclin D2

Granulosa cell tumors of the ovary (GCT) are the predominant type of ovarian sex cord/stromal tumor. Although prognosis is generally favorable, the outcome for advanced and recurrent GCT is poor. A better understanding of the molecular pathogenesis of GCT is critical to developing effective therapeutic strategies. Here we have examined the potential role of the runt-related transcription factor RUNX3. There are only two GCT cell lines available. While RUNX3 is silenced in the GCT cell line KGN cells, it is highly expressed in another GCT cell line, COV434 cells. Re-expression of RUNX3 promotes proliferation, anchorage-independent growth, and motility in KGN cells in vitro and tumor formation in mice in vivo. Furthermore, expression of a dominant negative form of RUNX3 decreases proliferation of COV434 cells. To address a potential mechanism of action, we examined expression of cyclin D2 and the CDK inhibitor p27Kip1, two cell cycle regulators known to be critical determinants of GCT cell proliferation. We found that RUNX3 upregulates the expression of cyclin D2 at the mRNA and protein level, and decreases the level of the p27Kip1 protein, but not p27Kip1 mRNA. In conclusion, we demonstrate that RUNX proteins are expressed in GCT cell lines and human GCT specimens, albeit at variable levels, and RUNX3 may play an oncogenic role in a subset of GCTs.

Tumorigenicity of herpesvirus-transformed cells correlates with production of plasminogen activator

1981 ◽  
Vol 1 (5) ◽  
pp. 408-417
Author(s):  
S F Adelman ◽  
M K Howett ◽  
F Rapp
Keyword(s):  
Cell Line ◽  
Plasminogen Activator ◽  
Cell Lines ◽  
Parental Cell ◽  
Tumor Formation ◽  
Parental Cell Line ◽  
Simplex Virus ◽  
Low Activity

Our studies first demonstrated that established hamster cell lines transformed in vitro by herpesviruses activate plasminogen more effectively than normal hamster fibroblasts. This ability is probably due to increased levels of the enzyme plasminogen activator (PA). In the studies described here, the 333-8-9 cell line, originally transformed by herpes simplex virus type 2 strain 333, was used to derive subclonal lines that maintained stable PA phenotypes over the course of long in vitro passage. We were interested in correlating tumor formation by the subclones with their fibrinolytic capacity. Cells were, therefore, single-cell subcloned twice, and resulting cultures were tested for ability to activate plasminogen in vitro. PA activity was then quantitated by [125I]fibrin lysis assay, and high- and low-activity subclones were isolated; these retained high- or low-activity phenotypes. Syngeneic newborn hamsters were inoculated with these subclones and observed for the appearance of palpable tumors. A strong correlation between enzyme activity and tumor formation was observed in four separate trials; animals receiving high-PA subclones developed tumors more rapidly than those inoculated with the parental cell line. Tumors were also excised from test animals, and the cell lines established from the tumors were tested in vitro at different passages for their ability to activate plasminogen. These tumor cells were then reinoculated into syngeneic animals to confirm the tumorigenicity of cell lines with high fibrinolytic activity. In these experiments, the positive correlation between PA production and tumorigenicity was confirmed.

Inactivation of the Suv39h1 Histone Methyltransferase Accelerates Myc-Driven B-Cell Lymphomagenesis and Compromises Drug-Inducible Cellular Senescence.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 235-235
Author(s):  
Soyoung Lee ◽  
Vedrana Tabor ◽  
Christoph Loddenkemper ◽  
Antoine H.F.M. Peters ◽  
Harald Stein ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
Cellular Senescence ◽  
Tumor Formation ◽  
Cellular Growth ◽  
Tunel Staining ◽  
Lymphoma Cells ◽  
Long Term Outcome

Abstract Activation of the myc oncogene is a frequent finding in human lymphomas. Acute induction of Myc in primary cells initiates massive apoptosis via the ARF/p53 pathway. In turn, apoptotic defects strongly collaborate with Myc in tumor formation. Previous work in a transgenic mouse model demonstrated that DNA damaging drugs can force apoptotically-compromised Myc-lymphomas to enter a terminal cell-cycle arrest, termed cellular senescence, which prolonged overall survival of the tumor-bearing animals. Recently, we identified the histone H3 lysine 9 (H3K9) methyltransferase Suv39h1 as a critical mediator of cellular senescence that acts as an early barrier against Ras-initiated lymphomagenesis, raising the question whether Myc-driven formation of lymphomas and their treatment sensitivity may depend on Suv39h1 function. Eμ-myc transgenic mice were intercrossed to mice harboring targeted deletions in the Suv39h1 locus. Myc transgenic mice with no additional defined genetic lesions - hereafter referred to as controls - developed B-cell lymphomas with a median onset of more than 100 days, while mice lacking one or both Suv39h1 alleles produced lymphomas significantly earlier, i.e. at a median age of less than 60 days. Importantly, lymphomas arising in female myc transgenic Suv39h1+/− mice invariably lost expression of the X-linked Suv39h1 gene. TUNEL staining in situ and short-term cytotoxicity assays in response to the DNA damaging compound adriamycin in vitro expectedly demonstrated no overt difference in spontaneous or drug-inducible apoptosis in control versus Suv39h1-deficient Myc-lymphomas. However, when the fractions of Myc-driven lymphoma cells in cycle where assessed by Ki67 staining in situ, absence of Suv39h1 allowed Myc to keep nearly all cells in cycle, while a substantial fraction of non-apoptotic control lymphoma cells apparently had exited the cycle. Accordingly, adriamycin-treatment in vitro produced a strong senescent phenotype in control cells in the presence of Bcl2, while no senescence response could be provoked in Suv39h1-deficient cells. Our findings provide novel insights into Myc-related deregulation of cellular growth control and senescence as a tumor suppressor mechanism, and have important ramifications for the therapeutic utilization of DNA-damage effector programs such as apoptosis and cellular senescence. Whether Suv39h1 inactivation impacts on the long-term outcome of cancer therapy in vivo is currently under investigation and will be reported at the meeting.

scholarly journals Tumorigenicity of herpesvirus-transformed cells correlates with production of plasminogen activator.

1981 ◽  
Vol 1 (5) ◽  
pp. 408-417 ◽  
Author(s):  
S F Adelman ◽  
M K Howett ◽  
F Rapp
Keyword(s):  
Cell Line ◽  
Plasminogen Activator ◽  
Cell Lines ◽  
Parental Cell ◽  
Tumor Formation ◽  
Parental Cell Line ◽  
Simplex Virus ◽  
Low Activity

Our studies first demonstrated that established hamster cell lines transformed in vitro by herpesviruses activate plasminogen more effectively than normal hamster fibroblasts. This ability is probably due to increased levels of the enzyme plasminogen activator (PA). In the studies described here, the 333-8-9 cell line, originally transformed by herpes simplex virus type 2 strain 333, was used to derive subclonal lines that maintained stable PA phenotypes over the course of long in vitro passage. We were interested in correlating tumor formation by the subclones with their fibrinolytic capacity. Cells were, therefore, single-cell subcloned twice, and resulting cultures were tested for ability to activate plasminogen in vitro. PA activity was then quantitated by [125I]fibrin lysis assay, and high- and low-activity subclones were isolated; these retained high- or low-activity phenotypes. Syngeneic newborn hamsters were inoculated with these subclones and observed for the appearance of palpable tumors. A strong correlation between enzyme activity and tumor formation was observed in four separate trials; animals receiving high-PA subclones developed tumors more rapidly than those inoculated with the parental cell line. Tumors were also excised from test animals, and the cell lines established from the tumors were tested in vitro at different passages for their ability to activate plasminogen. These tumor cells were then reinoculated into syngeneic animals to confirm the tumorigenicity of cell lines with high fibrinolytic activity. In these experiments, the positive correlation between PA production and tumorigenicity was confirmed.

scholarly journals The Lysine-rich C-terminal Tail of Heparin Affin Regulatory Peptide Is Required for Mitogenic and Tumor Formation Activities

2001 ◽  
Vol 276 (15) ◽  
pp. 12228-12234 ◽  
Author(s):  
Isabelle Bernard-Pierrot ◽  
Jean Delbé ◽  
Danièle Caruelle ◽  
Denis Barritault ◽  
José Courty ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Biological Activities ◽  
Chinese Hamster ◽  
Tumor Formation ◽  
Cellular Growth ◽  
Heparin Binding ◽  
Regulatory Peptide ◽  
Peptide Cleavage ◽  
Terminal Domain

Heparin affin regulatory peptide (HARP) is a 18-kDa heparin-binding polypeptide that is highly expressed in developing tissues and in several primary human tumors. It seems to play a key role in cellular growth and differentiation.In vitro, HARP displays mitogenic, angiogenic, and neurite outgrowth activities. It is a secreted protein that is organized in two β-sheet domains, each domain containing a cluster of basic residues. To assess determinants involved in the biological activities of HARP, C-terminally truncated proteins were produced in Chinese hamster ovary-K1 cells and tested for their mitogenic, tumor formation in nude mice and neurite outgrowth activities. Our data clearly indicate that the residues 111–136 of the lysine-rich C-terminal domain are involved in the mitogenic and tumor formation activities of HARP. Correlatively, no signal transduction was detected using the corresponding mutant, suggesting the absence of HARP binding to its high affinity receptor. However, this C-terminal domain of HARP is not involved in the neurite outgrowth activity. We also demonstrate that HARP signal peptide cleavage could led to two maturated forms that are both but differentially mitogenic.

scholarly journals Physical Characterization of Colorectal Cancer Spheroids and Evaluation of NK Cell Infiltration Through a Flow-Based Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Azzurra Sargenti ◽  
Francesco Musmeci ◽  
Francesco Bacchi ◽  
Cecilia Delprete ◽  
Domenico Andrea Cristaldi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Culture ◽  
Cell Viability ◽  
Cell Line ◽  
Nk Cell ◽  
3D Cell Culture ◽  
Physical Characterization ◽  
Tumor Spheroids

To improve pathogenetic studies in cancer development and reliable preclinical testing of anti-cancer treatments, three-dimensional (3D) cultures, including spheroids, have been widely recognized as more physiologically relevant in vitro models of in vivo tumor behavior. Currently, the generation of uniformly sized spheroids is still challenging: different 3D cell culture methods produce heterogeneous populations in dimensions and morphology, that may strongly influence readouts reliability correlated to tumor growth rate or antitumor natural killer (NK) cell-mediated cytotoxicity. In this context, an increasing consensus claims the integration of microfluidic technologies within 3D cell culture, as the physical characterization of tumor spheroids is unavoidably demanded to standardize protocols and assays for in vitro testing. In this paper, we employed a flow-based method specifically conceived to measure weight, size and focused onto mass density values of tumor spheroids. These measurements are combined with confocal and digital imaging of such samples. We tested the spheroids of four colorectal cancer (CRC) cell lines that exhibit statistically relevant differences in their physical characteristics, even though starting from the same cell seeding density. These variations are seemingly cell line-dependent and associated with the number of growing cells and the degree of spheroid compaction as well, supported by different adenosine-triphosphate contents. We also showed that this technology can estimate the NK cell killing efficacy by measuring the weight loss and diameter shrinkage of tumor spheroids, alongside with the commonly used cell viability in vitro test. As the activity of NK cells relies on their infiltration rate, the in vitro sensitivity of CRC spheroids proved to be exposure time- and cell line-dependent with direct correlation to the cell viability reduction. All these functional aspects can be measured by the system and are documented by digital image analysis. In conclusion, this flow-based method potentially paves the way towards standardization of 3D cell cultures and its early adoption in cancer research to test antitumor immune response and set up new immunotherapy strategies.

scholarly journals Assessing Estrogen-Induced Proliferative Response in an Endometrial Cancer Cell Line Using a Universally Applicable Methodological Guide

2018 ◽  
Vol 28 (1) ◽  
pp. 122-133 ◽  
Author(s):  
Christina Parkes ◽  
Areege Kamal ◽  
Anthony J. Valentijn ◽  
Rafah Alnafakh ◽  
Stephane R. Gross ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Proliferative Response ◽  
Quantitative Polymerase Chain Reaction ◽  
Chorioallantoic Membrane ◽  
Tumor Formation ◽  
Membrane Model

ObjectiveTranslational endometrial cancer (EC) research benefits from an in vitro experimental approach using EC cell lines. We demonstrated the steps that are required to examine estrogen-induced proliferative response, a simple yet important research question pertinent to EC, and devised a pragmatic methodological workflow for using EC cell lines in experimental models.MethodsComprehensive review of all commercially available EC cell lines was carried out, and Ishikawa cell line was selected to study the estrogen responsiveness with HEC1A, RL95-2, and MFE280 cell lines as comparators where appropriate, examining relevant differential molecular (steroid receptors) and functional (phenotype, anchorage-independent growth, hormone responsiveness, migration, invasion, and chemosensitivity) characteristics in 2-dimensional and 3-dimensional cultures in vitro using immunocytochemistry, immunofluorescence, quantitative polymerase chain reaction, and Western blotting. In vivo tumor, formation, and chemosensitivity were also assessed in a chick chorioallantoic membrane model.ResultsShort tandem repeat analysis authenticated the purchased cell lines, whereas gifted cells deviated significantly from the published profile. We demonstrate the importance of prior assessment of the suitability of each cell line for the chosen in vitro experimental technique. Prior establishment of baseline, nonenriched conditions was required to induce a proliferative response to estrogen. The chorioallantoic membrane model was a suitable in vivo multicellular animal model for EC for producing rapid and reproducible data.ConclusionsWe have developed a methodological guide for EC researchers when using endometrial cell lines to answer important translational research questions (exemplified by estrogen-responsive cell proliferation) to facilitate robust data, while saving time and resources.

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