Influences of the 3D microenvironment on cancer cell behaviour and treatment responsiveness: A recent update on lung, breast and prostate cancer models

Costard, Lara S.; Hosn, Ryan R.; Ramanayake, Harumi; O’Brien, Fergal J.; Curtin, Caroline M.

doi:10.1016/j.actbio.2021.01.023

Cited by 27 publications

(29 citation statements)

References 164 publications

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“…Furthermore, cell models exhibited a significantly greater viability rate when cultured on 15%-PCL-ES platforms after 3 days. Pore size, surface availability, and porosity of 3D platforms as well as initial seeding cell density or time of culture, influence cell colonization [ 22 , 51 ]. The cell viability was also correlated to the protein adsorbed, which directly affected cell division [ 55 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

“…Monolayer culture does not fully mimic the tumor microenvironment where the extracellular matrix (ECM) has an essential role in some processes, for example gene expression and drug response. At the same time, cancer cells affect ECM deposition, degradation, and remodeling, influencing tumor progression and invasiveness [ 22 ]. Although 2D cell culture is a well-established, simple, and economical method, flat surfaces alter apical-basal polarity, nutrient and oxygen distribution, soluble gradients, and cell proliferation, morphology, and interactions [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…Chen et al highlighted that not only oncogenic changes but also the surrounding microenvironment are crucial for the definitive cell phenotype in lung adenocarcinoma [ 33 ]. Cell proliferation, genetic and protein expression, and response to drugs are modified in cells cultured on 3D models compared to monolayer culture [ 22 ]. Besides this, researchers have pointed out that mechanical signals induced by cell-generated physical force cause changes in cell morphology, adhesion, alignment, differentiation, and migration [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

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Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

Polonio‐Alcalá

Rabionet

Ruiz‐Martínez

et al. 2021

Cancers

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The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

Polonio‐Alcalá

Rabionet

Ruiz‐Martínez

et al. 2021

Cancers

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“…The critical role of breast TME in tumor growth and therapeutic response has been increasingly recognized, particularly as it relates to breast cancer metastatic progression. In recent years, various aspects of breast tumor TME has been extensively reviewed (Di Virgilio et al, 2018;Hamidi and Ivaska, 2018;Lim et al, 2018;Spranger and Gajewski, 2018;Costard et al, 2021), however, there is still much to be learned in our effort to develop novel therapies targeting the TME. Early stage microfluidic devices usually employ several parallel straight microchannels for easy access and imaging, therefore, is capable of studying cell migration (Wong et al, 2012), however, these devices have not been optimized for studying sophisticated interactions between tumor, endothelium, stroma, immune cells, chemokines, or cancer stem cells (Sridharan et al, 2019) observed in the complex TME.…”

Section: The Breast Tumor Microenvironmentmentioning

confidence: 99%

Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis

Sigdel

Gupta

Faizee

et al. 2021

Front. Bioeng. Biotechnol.

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Of around half a million women dying of breast cancer each year, more than 90% die due to metastasis. Models necessary to understand the metastatic process, particularly breast cancer cell extravasation and colonization, are currently limited and urgently needed to develop therapeutic interventions necessary to prevent breast cancer metastasis. Microfluidic approaches aim to reconstitute functional units of organs that cannot be modeled easily in traditional cell culture or animal studies by reproducing vascular networks and parenchyma on a chip in a three-dimensional, physiologically relevant in vitro system. In recent years, microfluidics models utilizing innovative biomaterials and micro-engineering technologies have shown great potential in our effort of mechanistic understanding of the breast cancer metastasis cascade by providing 3D constructs that can mimic in vivo cellular microenvironment and the ability to visualize and monitor cellular interactions in real-time. In this review, we will provide readers with a detailed discussion on the application of the most up-to-date, state-of-the-art microfluidics-based breast cancer models, with a special focus on their application in the engineering approaches to recapitulate the metastasis process, including invasion, intravasation, extravasation, breast cancer metastasis organotropism, and metastasis niche formation.

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“…While 2D studies have enabled better understanding of radiation responses of breast cancer cells, monolayer cultures are oversimplified and lack the complex 3D architecture of the TME. This would mean that they cannot recapitulate the intercellular, intracellular and cell-ECM interactions that determine the tumor growth, metastasis and response to targeted therapy [ 83 ]. Inadequacy of these models diminishes the potential of translating the findings to clinical settings.…”

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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Influences of the 3D microenvironment on cancer cell behaviour and treatment responsiveness: A recent update on lung, breast and prostate cancer models

Cited by 27 publications

References 164 publications

Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis

3D Breast Tumor Models for Radiobiology Applications

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