3D modeling in cancer studies

Atat, Oula El; Farzaneh, Zahra; Pourhamzeh, Mahsa; Taki, Fatima; Abi-Habib, Ralph J.; Vosough, Massoud; El‐Sibai, Mirvat

doi:10.1007/s13577-021-00642-9

Cited by 38 publications

(28 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This once more indicates the importance of 3D in vitro systems to mimic the in vivo tumor microenvironment and shows the weakness of monolayer approaches. The complex 3D conditions to which these cells are exposed, represent a realistic tissue architecture and therefore are more physiologically relevant (Pinto et al 2020 ; El Atat et al 2022 ; Rossi et al 2022 ). Except of the maximum size of the LDs, which was detected after 14 days of spheroid cultivation, we only found few differences between the different cultivation durations.…”

Section: Discussionmentioning

confidence: 99%

Lipid droplets and perilipins in canine osteosarcoma. Investigations on tumor tissue, 2D and 3D cell culture models

et al. 2022

View full text Add to dashboard Cite

Lipid droplets were identified as important players in biological processes of various tumor types. With emphasis on lipid droplet-coating proteins (perilipins, PLINs), this study intended to shed light on the presence and formation of lipid droplets in canine osteosarcoma. For this purpose, canine osteosarcoma tissue samples (n = 11) were analyzed via immunohistochemistry and electron microscopy for lipid droplets and lipid droplet-coating proteins (PLINs). Additionally, we used the canine osteosarcoma cell lines D-17 and COS4288 in 2D monolayer and 3D spheroid (cultivated for 7, 14, and 21 days) in vitro models, and further analyzed the samples by means of histochemistry, immunofluorescence, molecular biological techniques (RT-qPCR, Western Blot) and electron microscopical imaging. Lipid droplets, PLIN2, and PLIN3 were detected in osteosarcoma tissue samples as well as in 2D and 3D cultivated D-17 and COS4288 cells. In spheroids, specific distribution patterns of lipid droplets and perilipins were identified, taking into consideration cell line specific zonal apportionment. Upon external lipid supplementation (oleic acid), a rise of lipid droplet amount accompanied with an increase of PLIN2 expression was observed. Detailed electron microscopical analyzes revealed that lipid droplet sizes in tumor tissue were comparable to that of 3D spheroid models. Moreover, the biggest lipid droplets were found in the central zone of the spheroids at all sampling time-points, reaching their maximum size at 21 days. Thus, the 3D spheroids can be considered as a relevant in vitro model for further studies focusing on lipid droplets biology and function in osteosarcoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Lipid droplets and perilipins in canine osteosarcoma. Investigations on tumor tissue, 2D and 3D cell culture models

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Therefore, to understand the molecular mechanisms responsible for the spatially growing EMT changes in RPE cells, it becomes necessary to study the effects of both TGF-β2 and hypoxia, as possible major pathogenic inducers using a reliable 3D cell culture system that replicates such a spatial environment. In fact, in addition to the conventional 2D cell cultures, such an in vitro 3D spheroid model has been identified as a powerful tool for studying the molecular mechanisms of EMT as well as hypoxia within cancerous cells [ 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells

Suzuki

Sato

Watanabe

et al. 2022

IJMS

View full text Add to dashboard Cite

The hypoxia associated with the transforming growth factor-β2 (TGF-β2)-induced epithelial mesenchymal transition (EMT) of human retinal pigment epithelium (HRPE) cells is well recognized as the essential underlying mechanism responsible for the development of proliferative retinal diseases. In vitro, three-dimensional (3D) models associated with spontaneous O2 gradients can be used to recapitulate the pathological levels of hypoxia to study the effect of hypoxia on the TGF-β2-induced EMT of HRPE cells in detail, we used two-dimensional-(2D) and 3D-cultured HRPE cells. TGF-β2 and hypoxia significantly and synergistically increased the barrier function of the 2D HRPE monolayers, as evidenced by TEER measurements, the downsizing and stiffening of the 3D HRPE spheroids and the mRNA expression of most of the ECM proteins. A real-time metabolic analysis indicated that TGF-β2 caused a decrease in the maximal capacity of mitochondrial oxidative phosphorylation in the 2D HRPE cells, whereas, in the case of 3D HRPE spheroids, TGF-β2 increased proton leakage. The findings reported herein indicate that the TGF-β2-induced EMT of both the 2D and 3D cultured HRPE cells were greatly modified by hypoxia, but during these EMT processes, the metabolic plasticity was different between 2D and 3D HRPE cells, suggesting that the mechanisms responsible for the EMT of the HRPE cells may be variable during their spatial spreading.

show abstract

“…In contrast, we have recently shown that OXT increases the spheroid size in rat hypothalamic neurons (Salehi et al, 2021 ). The spheroid formation, proliferation, and cellular migration are being orchestrated by the cells’ ability to perform cell-cell contacts or cell-matrix interactions (Atat et al, 2022 ), cellular characteristics that are important hallmarks in degenerative disorders of the CNS or tumor formation in the periphery (Stadler et al, 2018 ; Atat et al, 2022 ). In this study, we have made use of the liposarcoma cell line MLS-402, which was virally transduced to overexpress a fluorescently labeled OXTR.…”

Section: Introductionmentioning

confidence: 99%

Oxytocin accelerates tight junction formation and impairs cellular migration in 3D spheroids: evidence from Gapmer-induced exon skipping

Jurek

Denk

Schäfer

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Oxytocin (OXT) is a neuropeptide that has been associated with neurological diseases like autism, a strong regulating activity on anxiety and stress-related behavior, physiological effects during pregnancy and parenting, and various cellular effects in neoplastic tissue. In this study, we aimed to unravel the underlying mechanism that OXT employs to regulate cell-cell contacts, spheroid formation, and cellular migration in a 3D culture model of human MLS-402 cells. We have generated a labeled OXT receptor (OXTR) overexpressing cell line cultivated in spheroids that were treated with the OXTR agonists OXT, Atosiban, and Thr4-Gly7-oxytocin (TGOT); with or without a pre-treatment of antisense oligos (Gapmers) that induce exon skipping in the human OXTR gene. This exon skipping leads to the exclusion of exon 4 and therefore a receptor that lost its intracellular G-protein-binding domain. Sensitive digital PCR (dPCR) provided us with the means to differentiate between wild type and truncated OXTR in our cellular model. OXTR truncation differentially activated intracellular signaling cascades related to cell-cell attachment and proliferation like Akt, ERK1/2-RSK1/2, HSP27, STAT1/5, and CREB, as assessed by a Kinase Profiler Assay. Digital and transmission electron microscopy revealed increased tight junction formation and well-organized cellular protrusions into an enlarged extracellular space after OXT treatment, resulting in increased cellular survival. In summary, OXT decreases cellular migration but increases cell-cell contacts and therefore improves nutrient supply. These data reveal a novel cellular effect of OXT that might have implications for degenerating CNS diseases and tumor formation in various tissues.

show abstract

3D modeling in cancer studies

Cited by 38 publications

References 130 publications

Lipid droplets and perilipins in canine osteosarcoma. Investigations on tumor tissue, 2D and 3D cell culture models

Lipid droplets and perilipins in canine osteosarcoma. Investigations on tumor tissue, 2D and 3D cell culture models

Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells

Oxytocin accelerates tight junction formation and impairs cellular migration in 3D spheroids: evidence from Gapmer-induced exon skipping

Contact Info

Product

Resources

About