The effects of size and shape of the ovarian cancer spheroids on the drug resistance and migration

Günay, Gökhan; Kirit, Hande A.; Kamatar, Advika; Baghdasaryan, Ofelya; Hamsici, Seren; Kirit, Hande Acar

doi:10.1016/j.ygyno.2020.09.002

Cited by 34 publications

(32 citation statements)

References 59 publications

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“…Spheroids can better reproduce tumor hypoxia, expression of extracellular matrix proteins, intracellular interactions, and growth factor exchanges [15][16][17]. In the literature, numerous examples of tumor cell line-derived spheroids can be found using different cancer cell lines, but only some include their evaluation against an anticancer drug [25,28,[31][32][33][34][35][36][37][38][39][40][41]53], which is usually a chemotherapeutic agent and not an anticancer peptide, as evaluated in this work. Additionally, a full characterization of the effect of therapeutics on apoptosis and ROS production is sometimes missing.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous 3D culture methods have been studied to generate these models based on (1) the application of automated forces (e.g., centrifugation, spinning, and rotation), (2) hydrogels, and (3) gravity (e.g., hanging drop culture, and liquid overlay culture) [28][29][30]. Based on these different techniques, researchers have been developing spheroids using different cancer cell types and matrices to accurately study chemotherapeutic drugs [28,[31][32][33][34][35][36][37][38][39][40][41].…”

Section: Introductionmentioning

confidence: 99%

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Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide

et al. 2021

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Breast cancer (BC) is the most commonly diagnosed cancer in women and one of the most common causes of cancer-related deaths. Despite intense research efforts, BC treatment still remains challenging. Improved drug development strategies are needed for impactful benefit to patients. Current preclinical studies rely mostly on cell-based screenings, using two-dimensional (2D) cell monolayers that do not mimic in vivo tumors properly. Herein, we explored the development and characterization of three-dimensional (3D) models, named spheroids, of the most aggressive BC subtypes (triple-negative breast cancer-TNBC; and human-epidermal growth receptor-2-HER2+), using the liquid overlay technique with several selected cell lines. In these cell line-derived spheroids, we studied cell density, proliferation, ultrastructure, apoptosis, reactive oxygen species (ROS) production, and cell permeabilization (live/dead). The results showed a formation of compact and homogeneous spheroids on day 7 after seeding 2000 cells/well for MDA-MB-231 and 5000 cells/well for BT-20 and BT-474. Next, we compared the efficacy of a model anticancer peptide (ACP) in cell monolayers and spheroids. Overall, the results demonstrated spheroids to be less sensitive to treatment than cell monolayers, revealing the need for more robust models in drug development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide

et al. 2021

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“…OVCAR-8 cells formed compact spheroids with high migratory capacity compared to the loose aggregates obtained from OVCAR-3 cells ( Figure 3 A). Moreover, spheroids displayed size-independent resistance against anti-cancer drugs [ 85 ]. Nectin-4 peptides inhibited the formation of OVCAR-5 and CAOV3 spheroids, suggesting that their addition to chemotherapeutic agents may increase the efficacy of maintaining cells as single cells or small aggregates [ 86 ].…”

Section: 3d Ovarian Cancer Modelsmentioning

confidence: 99%

“…Standardized protocols need to be established to assist researchers in generating MCTs with uniform sizes and for high-throughput assays [ 129 , 135 ]. A major limitation is that not all cell lines are capable of forming spheroids or aggregates, while those that generate spheroids can present different morphologies depending on the technique ( Table 1 ), thus, affecting their migratory capacity and chemoresistance [ 85 , 133 , 141 , 142 ]. The addition of a matrix using scaffolds (e.g., hydrogels) will allow spheroids to develop their own ECM and create more relevant 3D models similar to the tumors seen in patients.…”

Section: 3d Ovarian Cancer Modelsmentioning

confidence: 99%

“…( A ) An example of the formation of loose and compact aggregates using OVCAR-3 and OVCAR-8 cells, respectively. Samples were stained at the end of 6 days using F-actin (red) and nuclear marker DAPI (blue) (Reprinted from [ 85 ], Copyright © (2020), with permission from Elsevier). ( B ) An example of the establishment of organoids derived from patient-derived xenografts from tumor deposits in the peritoneum.…”

Section: Figurementioning

confidence: 99%

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Modeling the Tumor Microenvironment of Ovarian Cancer: The Application of Self-Assembling Biomaterials

Mendoza-Martinez

Loessner

Mata

et al. 2021

Cancers

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Ovarian cancer (OvCa) is one of the leading causes of gynecologic malignancies. Despite treatment with surgery and chemotherapy, OvCa disseminates and recurs frequently, reducing the survival rate for patients. There is an urgent need to develop more effective treatment options for women diagnosed with OvCa. The tumor microenvironment (TME) is a key driver of disease progression, metastasis and resistance to treatment. For this reason, 3D models have been designed to represent this specific niche and allow more realistic cell behaviors compared to conventional 2D approaches. In particular, self-assembling peptides represent a promising biomaterial platform to study tumor biology. They form nanofiber networks that resemble the architecture of the extracellular matrix and can be designed to display mechanical properties and biochemical motifs representative of the TME. In this review, we highlight the properties and benefits of emerging 3D platforms used to model the ovarian TME. We also outline the challenges associated with using these 3D systems and provide suggestions for future studies and developments. We conclude that our understanding of OvCa and advances in materials science will progress the engineering of novel 3D approaches, which will enable the development of more effective therapies.

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Biomaterial-Based Delivery Systems for Chemotherapeutics

Gugulothu

Dhawan

Sachdeva

et al. 2023

Targeted Cancer Therapy in Biomedical Engineering

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The effects of size and shape of the ovarian cancer spheroids on the drug resistance and migration

Cited by 34 publications

References 59 publications

Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide

Development of Breast Cancer Spheroids to Evaluate Cytotoxic Response to an Anticancer Peptide

Modeling the Tumor Microenvironment of Ovarian Cancer: The Application of Self-Assembling Biomaterials

Biomaterial-Based Delivery Systems for Chemotherapeutics

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