Desmoplastic Crosstalk in Pancreatic Ductal Adenocarcinoma Is Reflected by Different Responses of Panc-1, MIAPaCa-2, PaTu-8902, and CAPAN-2 Cell Lines to Cancer-associated/Normal Fibroblasts

Novák, S; Kolář, Michal; Szabó, Árpád; Vernerová, Z; Lacina, Lukáš; Strnad, Hynek; Šáchová, Jana; Hradilová, Miluše; Havránek, Jan; Španko, Michal; Čoma, Matúš; Urban, Lukáš; Kaňuchová, Miriam; Melegová, Nikola; Gürlich, R; Dvořák, Josef; Smetana, Karel; Gál, Péter; Szabó, Pavol

doi:10.21873/cgp.20254

Cited by 11 publications

(11 citation statements)

References 68 publications

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“…Currently, it is understood from numerous reviews that IL-6 production is not limited exclusively to immune cells but can also be synthesised by parenchymal cells of the skin, intestinal tract, smooth muscle, lung tissue, or stroll cells such as mesenchymal cells and fibroblasts [ 3 , 6 ]. Release of IL-6 from these stromal cells, such as fibroblasts, is depicted in Figure 1 based on Novák et al [ 7 ] and the author’s unpublished data. Pathologically, IL-6 is produced by tumour stromal cells, immune cells, trafficking to the cancerous lesion, or the cancer cells themselves ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities

Rašková

Lacina

Kejík

et al. 2022

Cells

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Interleukin 6 (IL-6) belongs to a broad class of cytokines involved in the regulation of various homeostatic and pathological processes. These activities range from regulating embryonic development, wound healing and ageing, inflammation, and immunity, including COVID-19. In this review, we summarise the role of IL-6 signalling pathways in cancer biology, with particular emphasis on cancer cell invasiveness and metastasis formation. Targeting principal components of IL-6 signalling (e.g., IL-6Rs, gp130, STAT3, NF-κB) is an intensively studied approach in preclinical cancer research. It is of significant translational potential; numerous studies strongly imply the remarkable potential of IL-6 signalling inhibitors, especially in metastasis suppression.

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Section: Introductionmentioning

confidence: 99%

The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities

Rašková

Lacina

Kejík

et al. 2022

Cells

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“…As was demonstrated in vitro, the production of IL-6 by CAFs is precisely controlled in the co-culture of cell lines from the ductal cancer of the pancreas and CAFs isolated from the same cancer type [39]. However, IL-6 should also be seen as a principal component of the senescence-associated secretory phenotype in many cells [115].…”

Section: Production Of Bioactive Factors With Emphasis On Il-6mentioning

confidence: 87%

“…In some types of cancer, CAFs are numerous and extensively produce the extracellular matrix. This is a prominent feature in, e.g., highly malignant ductal adenocarcinoma of the pancreas, referred to as the desmoplastic type of tumour [39,40]. On the other hand, the proportion of stromal cells is usually somewhat modest in cutaneous malignant melanoma [34] or glioblastoma [41].…”

Section: Fibroblasts As a Fundamental Bioactive Part Of The Majority ...mentioning

confidence: 99%

Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

Vokurka

Lacina

Brábek

et al. 2022

IJMS

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Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.

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“…The stroma is biologically highly active and significantly influences tumor growth, metastatic spread, and resistance to therapy [ 4 ]. Therefore, it is likely that CAFs influence the biology of PDAC through several mechanisms [ 5 , 6 , 7 ]. Primarily, CAFs influence malignant cells across a plethora of tumor types [ 8 ], including PDAC, by their paracrine production.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, miR-21 and miR-210 proved to have a certain diagnostic/prognostic value [ 14 , 16 , 17 ]. Our previous work addressed the expression profiles of normal fibroblasts and PANF at the whole-genome scale [ 5 ]. In this study, we focus on miRNA detection with emphasis on genes that have a functional relevance to miRNA expression and thus to the biology of PDAC.…”

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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Desmoplastic Crosstalk in Pancreatic Ductal Adenocarcinoma Is Reflected by Different Responses of Panc-1, MIAPaCa-2, PaTu-8902, and CAPAN-2 Cell Lines to Cancer-associated/Normal Fibroblasts

Cited by 11 publications

References 68 publications

The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities

The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities

Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

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

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