Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin

Azimi, Tayebeh; Loizidou, Marilena; Dwek, Miriam

doi:10.1038/s41598-020-68999-9

Cited by 35 publications

(27 citation statements)

References 52 publications

(52 reference statements)

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“…In accordance with other recent evidence collected in different models of 3D-perfused cancer cell culture, 2 , 3 , 22 , 23 , 40 we show that cell proliferation and viability were improved by perfusion at prolonged days of culture, when it is likely that the observed increased number of cells created competition for nutrients and oxygen (Figs. 2 , 3 ).…”

Section: Discussionsupporting

confidence: 93%

Perfusion Flow Enhances Viability and Migratory Phenotype in 3D-Cultured Breast Cancer Cells

et al. 2021

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Conventional 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.

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Section: Discussionsupporting

confidence: 93%

Perfusion Flow Enhances Viability and Migratory Phenotype in 3D-Cultured Breast Cancer Cells

et al. 2021

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“…The tumoroid model can be used in combination with other systems to increase stromal biomimicry. Azimi et al (2020) within the Dwek lab at University of Westminster have successfully demonstrated that flow induces an aggressive cancer phenotype with a reduced responsiveness to doxorubicin.…”

Section: Tumoroidsmentioning

confidence: 99%

3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness

Pape

Emberton

Cheema

2021

Front. Bioeng. Biotechnol.

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The use of tissue-engineered 3D models of cancer has grown in popularity with recent advances in the field of cancer research. 3D models are inherently more biomimetic compared to 2D cell monolayers cultured on tissue-culture plastic. Nevertheless 3D models still lack the cellular and matrix complexity of native tissues. This review explores different 3D models currently used, outlining their benefits and limitations. Specifically, this review focuses on stiffness and collagen density, compartmentalization, tumor-stroma cell population and extracellular matrix composition. Furthermore, this review explores the methods utilized in different models to directly measure cancer invasion and growth. Of the models evaluated, with PDX and in vivo as a relative “gold standard”, tumoroids were deemed as comparable 3D cancer models with a high degree of biomimicry, in terms of stiffness, collagen density and the ability to compartmentalize the tumor and stroma. Future 3D models for different cancer types are proposed in order to improve the biomimicry of cancer models used for studying disease progression.

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“…More importantly, the breast cancer cell lines showed resistance to chemotherapy (Paclitaxel) with more surviving cells upon shear stimulation [ 129 ]. In a similar study, Azimi et al demonstrated a reduction in 3D breast cancer sensitivity to Doxorubicin in the presence of a fluid flow environment [ 130 ]. With these studies indicating the role of fluid flow on breast cancer metastasis and resistance to chemotherapy, its effects on radiation response remains unanswered.…”

Section: Current Preclinical Tools To Evaluate Effects Of Radiation Therapymentioning

confidence: 99%

3D Breast Tumor Models for Radiobiology Applications

Ravichandran

Clegg

Adams

et al. 2021

Cancers

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Breast cancer is a leading cause of cancer-associated death in women. The clinical management of breast cancers is normally carried out using a combination of chemotherapy, surgery and radiation therapy. The majority of research investigating breast cancer therapy until now has mainly utilized two-dimensional (2D) in vitro cultures or murine models of disease. However, there has been significant uptake of three-dimensional (3D) in vitro models by cancer researchers over the past decade, highlighting a complimentary model for studies of radiotherapy, especially in conjunction with chemotherapy. In this review, we underline the effects of radiation therapy on normal and malignant breast cells and tissues, and explore the emerging opportunities that pre-clinical 3D models offer in improving our understanding of this treatment modality.

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Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin

Cited by 35 publications

References 52 publications

Perfusion Flow Enhances Viability and Migratory Phenotype in 3D-Cultured Breast Cancer Cells

Perfusion Flow Enhances Viability and Migratory Phenotype in 3D-Cultured Breast Cancer Cells

3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness

3D Breast Tumor Models for Radiobiology Applications

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