Nejvíce citovaný článek - PubMed ID 34837514
Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts
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.
- Klíčová slova
- IL-6, cancer-associated fibroblast, hypoxia, miR-21, miR-210, miRNA, pancreas,
- MeSH
- diabetes mellitus MeSH
- duktální karcinom pankreatu * patologie MeSH
- faciální stigmatizace MeSH
- fibroblasty asociované s nádorem * metabolismus MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- mozeček abnormality MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní * patologie MeSH
- regulace genové exprese u nádorů MeSH
- růstová retardace plodu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA * MeSH
- MIRN217 microRNA, human MeSH Prohlížeč
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.
- Klíčová slova
- IL-6, cancer, metastasis,
- MeSH
- antitumorózní látky * terapeutické užití MeSH
- interleukin-6 metabolismus MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antitumorózní látky * MeSH
- IL6 protein, human MeSH Prohlížeč
- interleukin-6 MeSH
Recent evidence indicates that targeting IL-6 provides broad therapeutic approaches to several diseases. In patients with cancer, autoimmune diseases, severe respiratory infections [e.g. coronavirus disease 2019 (COVID-19)] and wound healing, IL-6 plays a critical role in modulating the systemic and local microenvironment. Elevated serum levels of IL-6 interfere with the systemic immune response and are associated with disease progression and prognosis. As already noted, monoclonal antibodies blocking either IL-6 or binding of IL-6 to receptors have been used/tested successfully in the treatment of rheumatoid arthritis, many cancer types, and COVID-19. Therefore, in the present review, we compare the impact of IL-6 and anti-IL-6 therapy to demonstrate common (pathological) features of the studied diseases such as formation of granulation tissue with the presence of myofibroblasts and deposition of new extracellular matrix. We also discuss abnormal activation of other wound-healing-related pathways that have been implicated in autoimmune disorders, cancer or COVID-19.
- Klíčová slova
- Cancer stroma, Granulation tissue, IL-6, Inflammation, Myofibroblast, Peripheral nerve injury, Rheumatoid arthritis, SARS-CoV-2, Wound healing,
- MeSH
- autoimunita MeSH
- autoimunitní nemoci * farmakoterapie MeSH
- COVID-19 * MeSH
- hojení ran MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * farmakoterapie MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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.
- Klíčová slova
- IL-6, cancer ecosystem, cancer microenvironment, cancer-associated fibroblast, exosome,
- MeSH
- exozómy metabolismus MeSH
- fibroblasty asociované s nádorem metabolismus MeSH
- interleukin-6 metabolismus MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory metabolismus MeSH
- parakrinní signalizace MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- IL6 protein, human MeSH Prohlížeč
- interleukin-6 MeSH