Building in vitro 3D human multicellular models of high-grade serous ovarian cancer

Malacrida, Beatrice; Pearce, Oliver M.T.; Balkwill, Frances R.

doi:10.1016/j.xpro.2021.101086

Cited by 7 publications

(4 citation statements)

References 6 publications

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“…Indeed, adipocytes have been shown to increase proliferation and chemoresistance of EOC cells, and may constitute a preferential invasion site for floating aggregates [24,81,101,102]. On this basis, multi-cellular culture models were developed by Pearce and Balkwill [103][104][105]. In their study on the impact of platelets on extracellular matrix production and tissue invasion, they used a 3D model where fibroblasts were plated on top of a gel loaded with adipocytes, followed by a layer of mesothelial cells.…”

Section: Co-culture Which Cells?mentioning

confidence: 99%

In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models

et al. 2023

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Ovarian cancer (OC) is a disease of major concern with a survival rate of about 40% at five years. This is attributed to the lack of visible and reliable symptoms during the onset of the disease, which leads over 80% of patients to be diagnosed at advanced stages. This implies that metastatic activity has advanced to the peritoneal cavity. It is associated with both genetic and phenotypic heterogeneity, which considerably increase the risks of relapse and reduce the survival rate. To understand ovarian cancer pathophysiology and strengthen the ability for drug screening, further development of relevant in vitro models that recapitulate the complexity of OC microenvironment and dynamics of OC cell population is required. In this line, the recent advances of tridimensional (3D) cell culture and microfluidics have allowed the development of highly innovative models that could bridge the gap between pathophysiology and mechanistic models for clinical research. This review first describes the pathophysiology of OC before detailing the engineering strategies developed to recapitulate those main biological features.

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Section: Co-culture Which Cells?mentioning

confidence: 99%

In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models

et al. 2023

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“…129 Recently, Malacrida et al described the generation of tri-and tetra-culture of HGSC, where mesothelial cells, fibroblasts, and adipocytes were isolated from the patient's omentum and were then cultured with the tumor cells in adipocyte gel with or without collagen gel. 130 This model could allow experiments for up to 21-28 days. The authors used this model to elicit the interaction between platelet and mesothelial cells in tumor invasion.…”

Section: Co-culture Modelsmentioning

confidence: 99%

Patient‐derived organoid culture in epithelial ovarian cancers—Techniques, applications, and future perspectives

Chan,

Mo,

et al. 2023

Cancer Medicine

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Epithelial ovarian cancer (EOC) is a heterogeneous disease composed of different cell types with different molecular aberrations. Traditional cell lines and mice models cannot recapitulate the human tumor biology and tumor microenvironment (TME). Patient‐derived organoids (PDOs) are freshly derived from patients' tissues and are then cultured with extracellular matrix and conditioned medium. The high concordance of epigenetic, genomic, and proteomic landscapes between the parental tumors and PDOs suggests that PDOs can provide more reliable results in studying cancer biology, allowing high throughput drug screening, and identifying their associated signaling pathways and resistance mechanisms. However, despite having a heterogeneity of cells in PDOs, some cells in TME will be lost during the culture process. Next‐generation organoids have been developed to circumvent some of the limitations. Genetically engineered organoids involving targeted gene editing can facilitate the understanding of tumorigenesis and drug response. Co‐culture systems where PDOs are cultured with different cell components like immune cells can allow research using immunotherapy which is otherwise impossible in conventional cell lines. In this review, the limitations of the traditional in vitro and in vivo assays, the use of PDOs, the challenges including some tips and tricks of PDO generation in EOC, and the future perspectives, will be discussed.

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“…This powerful and unique co-culture model was utilized as a powerful and efficient therapeutics screening platform to identify novel compounds that block EOC cell adhesion and invasion [71]. Similarly, the Balkwill group established various tri-, tetra-and penta-cultures, also utilizing patient omental samples to isolate fibroblasts, adipocytes, and monocytes, to study the influence of omental components on HGSC cells and the deposition of ECM [72][73][74][75]. Using these patient-derived co-culture systems, both groups were able to faithfully recapitulate early and late steps of invasion through histological comparisons of their in vitro co-culture models to direct clinical specimens.…”

Section: Co-culture Model Systemsmentioning

confidence: 99%

Insights into high-grade serous carcinoma pathobiology using three-dimensional culture model systems

Tomas

Shepherd

2023

J Ovarian Res

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Epithelial ovarian cancer (EOC) research has become more complex as researchers try to fully understand the metastatic process. Especially as we delve into the concept of tumour dormancy, where cells transition between proliferative and dormant states to survive during disease progression. Thus, the in vitro models used to conduct this research need to reflect this vast biological complexity. The innovation behind the many three-dimensional (3D) spheroid models has been refined to easily generate reproducible spheroids so that we may understand the various molecular signaling changes of cells during metastasis and determine therapeutic efficacy of treatments. This ingenuity was then used to develop the 3D ex vivo patient-derived organoid model, as well as multiple co-culture model systems for EOC research. Although, researchers need to continue to push the boundaries of these current models for in vitro and even in vivo work in the future. In this review, we describe the 3D models already in use, where these models can be developed further and how we can use these models to gain the most knowledge on EOC pathogenesis and discover new targeted therapies.

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Building in vitro 3D human multicellular models of high-grade serous ovarian cancer

Cited by 7 publications

References 6 publications

In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models

In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models

Patient‐derived organoid culture in epithelial ovarian cancers—Techniques, applications, and future perspectives

Insights into high-grade serous carcinoma pathobiology using three-dimensional culture model systems

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