Biomaterial substrate-derived compact cellular spheroids mimicking the behavior of pancreatic cancer and microenvironment

Wong, Chui‐Wei; Han, Hao-Wei; Tien, Yu‐Wen; Hsu, Shan‐hui

doi:10.1016/j.biomaterials.2019.05.013

Cited by 53 publications

(25 citation statements)

References 66 publications

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“…HepG2 and HUVECs were spun down, resuspended, and then divided by 150 μL into wells of a U-shaped 96-well suspension plate (Greiner Bio-One, Stonehouse, UK). The plate was incubated at 37°C for 48 h to allow for spheroid formation (29). A laser scanning confocal microscope (ZEISS) was used to examine the structural organization of tumor spheroids.…”

Section: Methodsmentioning

confidence: 99%

YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA

Yang

Qin

et al. 2019

Front. Oncol.

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Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor malignancy of HCC. However, the relationship between YY1 and endothelial cell-dependent tumor angiogenesis in HCC remains unclear. In this study, we observed that YY1 is positively correlated with microvessel density (MVD) and poor prognosis in HCC tissues. We further found that YY1 promotes the transcriptional activity of VEGFA by binding its promoter in HCC. The secreted VEGFA from HCC cells activates phosphorylation of VEGFR2 to promotes tube formation, cell migration, and invasion of vascular endothelial cells in vitro, and promotes tumor growth and angiogenesis in vivo. In addition, upregulation of YY1 enhanced resistance of bevacizumab in HCC cells. These results indicate that YY1 plays essential roles in HCC angiogenesis and resistance of bevacizumab by inducing VEGFA transcription and that YY1 may represent a potential molecular target for antiangiogenic therapy during HCC progression.

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Section: Methodsmentioning

confidence: 99%

YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA

Yang

Qin

et al. 2019

Front. Oncol.

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“…A follow up study demonstrated that these cultured PDAC tissue slices have genomic stability with minimal transcriptome changes throughout the 72 hours of culture 25 . Several other studies have developed in vitro co-culture models containing tumour cells, cancer-associated fibroblasts (CAFs), and endothelial cells 26–30 , but these models do not perfectly mimic the in situ complexity and heterogeneity of human PDAC tumours. For example, an impressive study by Gupta et al 26 developed a coculture model of cancer cells, endothelial cells and CAFs on a polyurethane scaffold.…”

Section: Discussionmentioning

confidence: 99%

Bringing the pancreas patient back to the bench:Ex vivoculture of intact human patient derived pancreatic tumour tissue

Kokkinos

Sharbeen

Haghighi

et al. 2020

Preprint

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The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is attributed to the highly fibrotic stroma and complex multi-cellular microenvironment that is difficult to fully recapitulate in pre-clinical human models. To fast-track translation of therapies and to inform personalised medicine, we aimed to develop a whole-tissue ex vivo explant model that maintains viability, 3D multicellular architecture, and microenvironmental cues present in human pancreatic tumours. Patient-derived surgically-resected PDAC tissue was cut into 2 mm explants, cultured on gelatin sponges, and grown for 12 days. Immunohistochemistry revealed that human PDAC tissue explants were viable for 12 days and maintained their original tumour, stromal and extracellular matrix architecture. As proof-of-principle, human PDAC tissue explants responded to Abraxane® treatment with a 3.7-fold increase in cell-death (p=0.0007). PDAC explants were also transfected with polymeric nanoparticles+Cy5-siRNA and we observed abundant cytoplasmic distribution of nanoparticle+Cy5-siRNA throughout the PDAC explant tissue. Our novel model retains the 3D architecture of human pancreatic tumours and has several advantages over standard organoids: presence of functional multi-cellular stroma and fibrosis and no tissue manipulation, digestion, or artificial propagation of organoids. This provides an unprecedented opportunity to study PDAC biology, tumour-stromal interactions and rapidly assess therapeutic response that could drive personalised treatment for PDAC.

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“…Another aspect of co-culturing to take into account is the spatial organization of the cells in a spheroid. Wong et al as well as Firuzi et al observed that, in the co-culture of pancreatic cancer cells and PSC, the PSC forms the outer layer of the spheroid while the cancer cells form the core [ 41 , 68 ]. This contradicts the findings of Norberg et al describing the reverse case [ 64 ].…”

Section: Co-cultures Visualize Challenges Associated With Tumor–stmentioning

confidence: 99%

Three-Dimensional Cell Culture Systems in Radiopharmaceutical Cancer Research

Doctor

Seifert

Ullrich

et al. 2020

Cancers

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In preclinical cancer research, three-dimensional (3D) cell culture systems such as multicellular spheroids and organoids are becoming increasingly important. They provide valuable information before studies on animal models begin and, in some cases, are even suitable for reducing or replacing animal experiments. Furthermore, they recapitulate microtumors, metastases, and the tumor microenvironment much better than monolayer culture systems could. Three-dimensional models show higher structural complexity and diverse cell interactions while reflecting (patho)physiological phenomena such as oxygen and nutrient gradients in the course of their growth or development. These interactions and properties are of great importance for understanding the pathophysiological importance of stromal cells and the extracellular matrix for tumor progression, treatment response, or resistance mechanisms of solid tumors. Special emphasis is placed on co-cultivation with tumor-associated cells, which further increases the predictive value of 3D models, e.g., for drug development. The aim of this overview is to shed light on selected 3D models and their advantages and disadvantages, especially from the radiopharmacist’s point of view with focus on the suitability of 3D models for the radiopharmacological characterization of novel radiotracers and radiotherapeutics. Special attention is paid to pancreatic ductal adenocarcinoma (PDAC) as a predestined target for the development of new radionuclide-based theranostics.

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Biomaterial substrate-derived compact cellular spheroids mimicking the behavior of pancreatic cancer and microenvironment

Cited by 53 publications

References 66 publications

YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA

YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA

Bringing the pancreas patient back to the bench:Ex vivoculture of intact human patient derived pancreatic tumour tissue

Three-Dimensional Cell Culture Systems in Radiopharmaceutical Cancer Research

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