Clonogenicity of Cultured Prostate Cancer Cells Is Controlled by Dormancy: Significance and Comparison with Cell Culture Models of Breast Cancer Cell Dormancy

Author(s):  
Thierry Tchénio
2020 ◽  
Vol 21 (12) ◽  
pp. 4413 ◽  
Author(s):  
Austin R. Holub ◽  
Anderson Huo ◽  
Kavil Patel ◽  
Vishal Thakore ◽  
Pranav Chhibber ◽  
...  

Traditionally, two-dimensional (2D) monolayer cell culture models have been used to study in vitro conditions for their ease of use, simplicity and low cost. However, recently, three-dimensional (3D) cell culture models have been heavily investigated as they provide better physiological relevance for studying various disease behaviors, cellular activity and pharmaceutical interactions. Typically, small-sized tumor spheroid models (100–500 μm) are used to study various biological and physicochemical activities. Larger, millimetric spheroid models are becoming more desirable for simulating native tumor microenvironments (TMEs). Here, we assess the use of ultra-large spheroid models (~2000 μm) generated from scaffolds made from a nozzle-free, ultra-high resolution printer; these models are explored for assessing chemotherapeutic responses with molecular doxorubicin (DOX) and two analogues of DoxilⓇ (Dox-NPⓇ, DoxovesTM) on MDA-MB-231 and MCF-7 breast cancer cell lines. To provide a comparative baseline, small spheroid models (~500 μm) were developed using a self-aggregation method of MCF-7 breast cancer cell lines, and underwent similar drug treatments. Analysis of both large and small MCF-7 spheroids revealed that Dox-NP tends to have the highest level of inhibition, followed by molecular doxorubicin and then Doxoves. The experimental advantages and drawbacks of using these types of ultra-large spheroids for cancer research are discussed.


2018 ◽  
Vol 6 (25) ◽  
pp. 4223-4231 ◽  
Author(s):  
Jiacheng Zhao ◽  
Hongxu Lu ◽  
Yin Yao ◽  
Sylvia Ganda ◽  
Martina H. Stenzel

Internalization of rod-like micelles by breast cancer cells is significantly affected by the stiffness of nano-rods.


2019 ◽  
Vol 12 ◽  
pp. 194008291986426 ◽  
Author(s):  
Mohammed Al-Shehri ◽  
Mahmoud Moustafa

Aerva javanica (Burm.f.) Juss. ex Schult. (Amaranthaceae family) has many pharmaceutical properties. This study aimed to determine the anticancerous effect of A. javanica methanol extract (AJME) on breast cancer cell lines and prostate cancer cell lines. The antibacterial potency of A. javanica solvent extracts was tested against Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, and Shigella flexneri. A screening of five concentrations of A. javanica was done on prostate and breast cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The results showed that AJME had various levels of cytotoxicity toward both cancer cell lines. A significant decrease in the rate of cancer cells was associated with a higher concentration of the plant extract. The half maximal inhibitory concentration IC50 value was 4.50 μg/ml for the breast cancer cells and 14.51 μg/ml for the prostate cancer cells. The dried and fresh solvent extracts made with methanol and chloroform demonstrated maximum potency against all the tested pathogenic microbes. The petroleum ether and acetone extracts showed moderate activity, while the diethyl ether and hot water extracts had the lowest antibacterial activity. The gas chromatography-mass spectroscopy analysis showed that AJME had various chemical compounds that have many biological benefits. In conclusion, A. javanica is a promising candidate as a natural herb to treat cancers, more so in breast cancer than in prostate cancer, and it has potential as an antimicrobial agent against multidrug-resistant microbes.


Author(s):  
Alice Pasini ◽  
Joseph Lovecchio ◽  
Marilisa Cortesi ◽  
Chiara Liverani ◽  
Chiara Spadazzi ◽  
...  

AbstractConventional 2D cell culture, a traditional tool in pre-clinical studies, can hardly be regarded as a representation of a natural cell microenvironment. In this respect, it might result in altered cellular behaviors. To overcome such a limitation, different approaches have been tested to conduct more representative in vitro studies. In particular, the use of 3D cell culture introduces variables, such as cell-cell and cell-extracellular matrix interactions; cell features such as survival, proliferation and migration are consequently influenced. For an example, an enhanced drug resistance and increased invasiveness are shown by cancer cells when cultured in 3D versus 2D conventional culture models. In this setting however, non-uniform cell distribution and biological behaviors appear throughout the scaffold, due to reduced diffusion of oxygen and nutrients. Perfusion in bioreactor systems can be used to improve medium transport. In this line of reasoning, this study proposes a breast cancer cell culture model sustained by an integrated approach that couples a 3D environment and a fluid perfusion. This model improves viability and uniformness of cell distribution, while inducing morphological, functional and molecular cancer cell remodeling.


Micromachines ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 93
Author(s):  
Menekse Ermis ◽  
Ezgi Antmen ◽  
Ozgur Kuren ◽  
Utkan Demirci ◽  
Vasif Hasirci

In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and through that identification of the cancerous cells. In the last decade, cancer cells were studied on micropatterned substrates of varying sizes and with a variety of biomaterials. These studies were conducted using conventional cell culture plates carrying patterned films. In the present study, cell culture protocols were conducted in the clear-bottom micropatterned chip. This approach adds significantly to the current knowledge and applications by enabling low-volume and high-throughput processing of the cell behavior, especially the cell–micropattern interactions. In this study, two different breast cancer cell lines, MDA-MB-231 and MCF-7, were used. MDA-MB-231 cells are invasive and metastatic, while MCF-7 cells are not metastatic. The nuclei of these two cell types deformed to distinctly different levels on the micropatterns, had different metabolic and proliferation rates, and their cell cycles were affected. The Ch-Pattern chips developed in this study proved to have significant advantages when used in the biological analysis of live cells and highly beneficial in the study of screening breast cancer cell–substrate interactions in vitro.


2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.


2021 ◽  
Vol 22 (8) ◽  
pp. 4153
Author(s):  
Kutlwano R. Xulu ◽  
Tanya N. Augustine

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sukhneeraj P. Kaur ◽  
Arti Verma ◽  
Hee. K. Lee ◽  
Lillie M. Barnett ◽  
Payaningal R. Somanath ◽  
...  

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.


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