scholarly journals Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices

2018 ◽  
Vol 29 (14) ◽  
pp. 1704-1717 ◽  
Author(s):  
Anushree C. Gulvady ◽  
Fatemeh Dubois ◽  
Nicholas O. Deakin ◽  
Gregory J. Goreczny ◽  
Christopher E. Turner
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ectopic Expression ◽  
Three Dimensional ◽  
Cell Types ◽  
Cell Phenotype ◽  
In Vitro Invasiveness

The focal adhesion proteins Hic-5 and paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional (3D) extracellular matrices (ECMs). However, their respective roles in other cancer cell types have not been evaluated. Herein, utilizing 3D cell–derived matrices and fibronectin-coated one-dimensional substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity, and in vitro invasiveness. Domain mapping studies reveal sites critical to the functions of both Hic-5 and paxillin in regulating phenotype, while ectopic expression of Hic-5 in cell lines with low endogenous levels of the protein is sufficient to induce a Rac1-dependent mesenchymal phenotype and, in turn, increase amoeboid-mesenchymal plasticity and invasion. We show that the activity of vinculin, when coupled to the expression of Hic-5 is required for the mesenchymal morphology in the 3D ECM. Taken together, our results identify Hic-5 as a critical modulator of tumor cell phenotype that could be utilized in predicting tumor cell migratory and invasive behavior in vivo.

scholarly journals Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone–Tumor Niche

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 507
Author(s):  
Anne M. Hughes ◽  
Alexus D. Kolb ◽  
Alison B. Shupp ◽  
Kristy M. Shine ◽  
Karen M. Bussard
Keyword(s):  
Cancer Research ◽  
Tumor Cell ◽  
Cancer Cell ◽  
Bone Tumor ◽  
Metastatic Cancer ◽  
Critical Role ◽  
Three Dimensional ◽  
Biocompatible Materials

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone–tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. Three-dimensional bioprinting allows for the deposition of biocompatible materials and living cells in complex architectures, as well as provides a means to better replicate biological tissue niches in-vitro. In cancer research specifically, 3D constructs have been instrumental in seminal work modeling cancer cell dissemination to bone and bone–tumor cell crosstalk in the skeleton. Furthermore, the use of biocompatible materials, such as hydroxyapatite, allows for printing of bone-like microenvironments with the ability to be implanted and studied in in-vivo animal models. Moreover, the use of bioprinted models could drive the development of novel cancer therapies and drug delivery vehicles.

scholarly journals Cancer Cell Lines Are Useful Model Systems for Medical Research

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1098 ◽  
Author(s):  
Mirabelli ◽  
Coppola ◽  
Salvatore
Keyword(s):  
Medical Research ◽  
Cell Lines ◽  
Cancer Cell ◽  
Three Dimensional ◽  
Cancer Cell Lines ◽  
Culture Conditions ◽  
The Cancer Genome Atlas ◽  
Model Systems

Cell lines are in vitro model systems that are widely used in different fields of medical research, especially basic cancer research and drug discovery. Their usefulness is primarily linked to their ability to provide an indefinite source of biological material for experimental purposes. Under the right conditions and with appropriate controls, authenticated cancer cell lines retain most of the genetic properties of the cancer of origin. During the last few years, comparing genomic data of most cancer cell lines has corroborated this statement and those that were observed studying the tumoral tissue equivalents included in the The Cancer Genome Atlas (TCGA) database. We are at the disposal of comprehensive open access cell line datasets describing their molecular and cellular alterations at an unprecedented level of accuracy. This aspect, in association with the possibility of setting up accurate culture conditions that mimic the in vivo microenvironment (e.g., three-dimensional (3D) coculture), has strengthened the importance of cancer cell lines for continuing to sustain medical research fields. However, it is important to consider that the appropriate use of cell lines needs to follow established guidelines for guaranteed data reproducibility and quality, and to prevent the occurrence of detrimental events (i.e., those that are linked to cross-contamination and mycoplasma contamination)

scholarly journals A polyphenol-rich extract of Olive Mill Wastewater Enhances cancer chemotherapy effects while mitigating cardiac toxicity.

2021 ◽  
Author(s):  
Adriana Albini ◽  
Marco M. G. Festa ◽  
Nadja Ring ◽  
Denisa Baci ◽  
Michael Rehman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Heart Cells ◽  
Cancer Cell Growth ◽  
Rat Cardiomyocytes

Background. Cardiovascular toxicities still remain one of the most undesirable side effects in cancer patients receiving chemotherapy, and cardiotoxicity has been detected associated with many therapeutic regimens. A number of mechanisms are reported for these effects, some of which are related to inflammation, oxygen radical generation, mitochondrial damage. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, antioxidant activities which could exert protective effects on the heart cells. One very interesting derivative of EVOO preparation is represented by purified extract form waste waters. Here, we investigated the anti-cancer activity when combined with chemotherapeutics as well as potential cardioprotective activities of a polyphenol-rich extract from waste product of the EVOO, named A009. Methods and Results. Mice bearing prostate cancer (PCa) xenografts were treated with cisplatin with and without A009. Tumor cell growth was reduced by cis and by A009 and further hindered by the combination. The effects of the A009 extract on cardiovascular toxicities was investigated in vivo. The hearts of mice were analyzed, and the mitochondria were studied by transmission electron microscopy. A protection activity by A009 was observed. To confirm the in vivo data obtained with cisplatin therapy, tumor cell lines and rat cardiomyocytes were treated with cisplatin in vitro with and without A009. A009 enhanced cisplatin and 5FU reduced cancer cell growth while did not further affect co-treated rat cardiomyocytes. Another frequently used chemotherapeutic agent 5-fluorouracil (5FU), was also tested in this assay similar effects were observed. The cardioprotective effects of the A009 extract towards 5 FU chemotherapy were further investigated in a second system of in vitro cultures, on cardiomyocytes freshly isolated from mice pups. These cells were treated with 5-fluorouracil and A009. Wastewater extract mitigated the toxicity of the fluoropyrimidine. Conclusions. In vivo, we found synergisms of A009 and cisplatin in prostate cancer treatment. Hearts of mice xenografted with PCa cell lines and receiving co-treatment of A009 extracts along with cisplatin had reduced mitochondria damage compared to chemotherapy alone, indicating a cardioprotective role. A009 in vitro was additive to cisplatin and 5FU to reduce cancer cell growth while did not further affect rat cardiomyocytes cell cultures treated with cisplatin and 5FU. The A009 extract also rescued the proliferation rate of neonatal murine cardiomyocytes treated with 5-Fluorouracil. Our study demonstrates that the polyphenol-rich purified A009 extracts enhances the effect of chemotherapy in vitro and in vivo but mitigates effects on heart and heart cells. It could therefore represent a potential candidate for cardiovascular prevention in patients undergoing cancer chemotherapy.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

scholarly journals Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 92
Author(s):  
Bashir Lawal ◽  
Yen-Lin Liu ◽  
Ntlotlang Mokgautsi ◽  
Harshita Khedkar ◽  
Maryam Rachmawati Sumitra ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

Activation of the heat shock transcription factor by hypoxia in normal and tumor cell lines in vivo and in vitro

1992 ◽  
Vol 23 (4) ◽  
pp. 891-897 ◽  
Author(s):  
Amato J. Giaccia ◽  
Elizabeth A. Auger ◽  
Albert Koong ◽  
David J. Terris ◽  
Andrew I. Minchinton ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Tumor Cell ◽  
Cell Lines ◽  
Heat Shock Transcription Factor ◽  
Tumor Cell Lines

scholarly journals Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Xin Cai ◽  
Li Wu Zheng ◽  
Li Ma ◽  
Hong Zhang Huang ◽  
Ru Qing Yu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Nude Mice ◽  
Tongue Cancer ◽  
Cancer Cell Lines ◽  
Fluorescent Imaging ◽  
Cell Phenotype ◽  
Human Tongue

Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n=8). A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP) was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells’ tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

scholarly journals Identification of Prostaglandin F2 Receptor Negative Regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246197
Author(s):  
Jorge Marquez ◽  
Jianping Dong ◽  
Chun Dong ◽  
Changsheng Tian ◽  
Ginette Serrero
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Negative Regulator ◽  
Target Validation ◽  
Antibody Drug

Antibody-drug conjugates (ADC) are effective antibody-based therapeutics for hematopoietic and lymphoid tumors. However, there is need to identify new targets for ADCs, particularly for solid tumors and cancers with unmet needs. From a hybridoma library developed against cancer cells, we selected the mouse monoclonal antibody 33B7, which was able to bind to, and internalize, cancer cell lines. This antibody was used for identification of the target by immunoprecipitation and mass spectrometric analysis, followed by target validation. After target validation, 33B7 binding and target positivity were tested by flow cytometry and western blot analysis in several cancer cell lines. The ability of 33B7 conjugated to saporin to inhibit in vitro proliferation of PTFRN positive cell lines was investigated, as well as the 33B7 ADC in vivo effect on tumor growth in athymic mice. All flow cytometry and in vitro internalization assays were analyzed for statistical significance using a Welsh’s T-test. Animal studies were analyzed using Two-Way Analysis of Variance (ANOVA) utilizing post-hoc Bonferroni analysis, and/or Mixed Effects analysis. The 33B7 cell surface target was identified as Prostaglandin F2 Receptor Negative Regulator (PTGFRN), a transmembrane protein in the Tetraspanin family. This target was confirmed by showing that PTGFRN-expressing cells bound and internalized 33B7, compared to PTGFRN negative cells. Cells able to bind 33B7 were PTGFRN-positive by Western blot analysis. In vitro treatment PTGFRN-positive cancer cell lines with the 33B7-saporin ADC inhibited their proliferation in a dose-dependent fashion. 33B7 conjugated to saporin was also able to block tumor growth in vivo in mouse xenografts when compared to a control ADC. These findings show that screening antibody libraries for internalizing antibodies in cancer cell lines is a good approach to identify new cancer targets for ADC development. These results suggest PTGFRN is a possible therapeutic target via antibody-based approach for certain cancers.

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