Pancreatic ductal adenocarcinoma: tumor microenvironment and problems in the development of novel therapeutic strategies

Кузнецова, А. В.; Попова, О. П.; Панченков, Д. Н.; Dyuzheva, T. G.; Иванов, А. А.

doi:10.1007/s10238-022-00886-1

Cited by 9 publications

(8 citation statements)

References 154 publications

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“…The tumour microenvironment is universally recognized as a crucial factor for tumour initiation and central tumour targeting [ 44 ]. In addition, the extracellular matrix of PDAC, which is known as a mixture of numerous complicated compartments interacting to form a highly dense mass with an inefficient, leaky vascular network, is considered an important factor responsible for a low perfusion rate, which in turn causes a suboptimal microenvironment for drug delivery [ 45 , 46 , 47 , 48 ]. Recent studies on PDAC organoids have mainly relied on human tumour tissue or cell line-derived organoids cocultured with cancer-associated fibroblasts (CAFs) from patients.…”

Section: Applications Of Organoids In Pancreatic Cancermentioning

confidence: 99%

“…When cocultured with organoids, a divergence in CAFs may be observed among different organoids. CAFs form the main portion of the dense stroma, which is also a shelter of tumour cells that reproduce independently while prohibiting chemotherapy and targeted drugs from specialized elimination [ 47 ]. The extracellular matrix constitutes more than 90% of the tumour volume and interstitial cells, including myofibroblasts, CAFs, pancreatic stellate cells, and myeloid-derived suppressor cells.…”

Section: Applications Of Organoids In Pancreatic Cancermentioning

confidence: 99%

“…These cells interact with each other to create a stable stroma around the tumour mass [ 50 ]. The overlap of the extracellular matrix secreted by CAFs oppresses the tumour substance and induces tumour hypertension, resulting in the suppression of blood vessels inside the tumour and ultimately insufficient drug delivery [ 45 , 46 , 47 , 48 ]. Because fibroblasts create dense stroma-connected tissue around the mass, the PDAC organ is considered stiffer than the normal pancreas, and prohibits blood perfusion and drug delivery.…”

Section: Applications Of Organoids In Pancreatic Cancermentioning

confidence: 99%

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Pancreatic Organoids: A Frontier Method for Investigating Pancreatic-Related Diseases

Liu

Zhu

2023

IJMS

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The pancreas represents an important organ that has not been comprehensively studied in many fields. To fill this gap, many models have been generated, and traditional models have shown good performance in addressing pancreatic-related diseases, but are increasingly struggling to keep up with the need for further research due to ethical issues, genetic heterogeneity and difficult clinical translation. The new era calls for new and more reliable research models. Therefore, organoids have been proposed as a novel model for the evaluation of pancreatic-related diseases such as pancreatic malignancy, diabetes, and pancreatic cystic fibrosis. Compared with common traditional models, including 2D cell culture and gene editing mice, organoids derived from living humans or mice cause minimal harm to the donor, raise fewer ethical concerns, and reasonably address the claims of heterogeneity, which allows for the further development of pathogenesis studies and clinical trial analysis. In this review, we analyse studies on the use of pancreatic organoids in research on pancreatic-related diseases, discuss the advantages and disadvantages, and hypothesize future trends.

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Section: Applications Of Organoids In Pancreatic Cancermentioning

confidence: 99%

Section: Applications Of Organoids In Pancreatic Cancermentioning

confidence: 99%

Section: Applications Of Organoids In Pancreatic Cancermentioning

confidence: 99%

See 1 more Smart Citation

Pancreatic Organoids: A Frontier Method for Investigating Pancreatic-Related Diseases

Liu

Zhu

2023

IJMS

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“…The structural roles of CAFs include the production and simultaneous remodelling of the extracellular matrix [ 2 , 3 ]. Concerning the proportion of distinct cell types present in PDAC tumors, CAFs represent an outstandingly abundant cell type.…”

Section: Introductionmentioning

confidence: 99%

Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma

Mandys

Popov

Gürlich

et al. 2023

IJMS

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Therapy for pancreatic ductal adenocarcinoma remains challenging, and the chances of a complete cure are very limited. As in other types of cancer, the expression and role of miRNAs in controlling the biological properties of this type of tumor have been extensively studied. A better insight into miRNA biology seems critical to refining diagnostics and improving their therapeutic potential. In this study, we focused on the expression of miR-21, -96, -196a, -210, and -217 in normal fibroblasts, cancer-associated fibroblasts prepared from a ductal adenocarcinoma of the pancreas, and pancreatic carcinoma cell lines. We compared these data with miRNAs in homogenates of paraffin-embedded sections from normal pancreatic tissues. In cancer-associated fibroblasts and cancer cell lines, miRNAs differed significantly from the normal tissue. In detail, miR-21 and -210 were significantly upregulated, while miR-217 was downregulated. Similar transcription profiles were earlier reported in cancer-associated fibroblasts exposed to hypoxia. However, the cells in our study were cultured under normoxic conditions. We also noted a relation to IL-6 production. In conclusion, cultured cancer-associated fibroblasts and carcinoma cells reflect miR-21 and -210 expression similarly to the cancer tissue samples harvested from the patients.

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“…Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer ( 8 ) for which Geyer et al. evaluated the impact of the tumor stromal components on immune cell distribution and recruitment in a PDAC advanced preclinical model.…”

mentioning

confidence: 99%

Editorial: Organoids, organs-on-chip, nanoparticles and in silico approaches to dissect the tumor-immune dynamics and to unveil the drug resistance mechanisms to therapy in the tumor microenvironment

2023

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Pancreatic ductal adenocarcinoma: tumor microenvironment and problems in the development of novel therapeutic strategies

Cited by 9 publications

References 154 publications

Pancreatic Organoids: A Frontier Method for Investigating Pancreatic-Related Diseases

Pancreatic Organoids: A Frontier Method for Investigating Pancreatic-Related Diseases

Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma

Editorial: Organoids, organs-on-chip, nanoparticles and in silico approaches to dissect the tumor-immune dynamics and to unveil the drug resistance mechanisms to therapy in the tumor microenvironment

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