Fibroblasts, the most abundant cell type in the human body, play crucial roles in biological processes such as inflammation and cancer progression. They originate from the mesoderm or neural-crest-derived ectomesenchyme. Ectomesenchyme-derived fibroblasts contribute to facial formation and do not express HOX genes during development. The expression and role of the HOX genes in adult fibroblasts is not known. We investigated whether the developmental pattern persists into adulthood and under pathological conditions, such as cancer. We collected adult fibroblasts of ectomesenchymal and mesodermal origins from distinct body parts. The isolated fibroblasts were characterised by immunocytochemistry, and their transcriptome was analysed by whole genome profiling. Significant differences were observed between normal fibroblasts from the face (ectomesenchyme) and upper limb (mesoderm), particularly in genes associated with limb development, including HOX genes, e.g., HOXA9 and HOXD9. Notably, the pattern of HOX gene expression remained consistent postnatally, even in fibroblasts from pathological tissues, including inflammatory states and cancer-associated fibroblasts from primary and metastatic tumours. Therefore, the distinctive HOX gene expression pattern can serve as an indicator of the topological origin of fibroblasts. The influence of cell position and HOX gene expression in fibroblasts on disease progression warrants further investigation.

• Klíčová slova
• Cancer-associated fibroblasts, Ectomesenchyme, Expression pattern, Fibroblasts, Homeobox genes, Mesoderm,
• MeSH
• dospělí MeSH
• fibroblasty * metabolismus   cytologie   MeSH
• homeoboxové geny MeSH
• homeodoménové proteiny metabolismus   genetika   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezoderm * metabolismus   cytologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• homeodoménové proteiny MeSH

Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.

• Klíčová slova
• IL-6, cancer-associated fibroblasts, granulation tissue, myofibroblasts, wound healing,
• MeSH
• autoimunita * MeSH
• hojení ran * imunologie   MeSH
• interleukin-6 * metabolismus   imunologie   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * imunologie   metabolismus   patologie   MeSH
• stárnutí * imunologie   MeSH
• zánět * imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• interleukin-6 * MeSH

BACKGROUND: Embryos are regeneration and wound healing masters. They rapidly close wounds and scarlessly remodel and regenerate injured tissue. Regeneration has been extensively studied in many animal models using new tools such as single-cell analysis. However, until now, they have been based primarily on experiments assessing from 1 day post injury. RESULTS: In this paper, we reveal that critical steps initiating regeneration occur within hours after injury. We discovered the regeneration initiating cells (RICs) using single-cell and spatial transcriptomics of the regenerating Xenopus laevis tail. RICs are formed transiently from the basal epidermal cells, and their expression signature suggests they are important for modifying the surrounding extracellular matrix thus regulating development. The absence or deregulation of RICs leads to excessive extracellular matrix deposition and defective regeneration. CONCLUSION: RICs represent a newly discovered transient cell state involved in the initiation of the regeneration process.

• Klíčová slova
• Xenopus laevis, RICs, ROCs, Regeneration,
• MeSH
• analýza jednotlivých buněk MeSH
• extracelulární matrix metabolismus   MeSH
• hojení ran MeSH
• ocas * MeSH
• regenerace * MeSH
• transkriptom MeSH
• Xenopus laevis * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články 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

Heterogeneous spheroids have recently acquired a prominent position in melanoma research because they incorporate microenvironmental cues relevant for melanoma. In this study, we focused on the analysis of microenvironmental factors introduced in melanoma heterogeneous spheroids by different dermal fibroblasts. We aimed to map the fibroblast diversity resulting from previously acquired damage caused by exposure to extrinsic and intrinsic stimuli. To construct heterogeneous melanoma spheroids, we used normal dermal fibroblasts from the sun-protected skin of a juvenile donor. We compared them to the fibroblasts from the sun-exposed photodamaged skin of an adult donor. Further, we analysed the spheroids by single-cell RNA sequencing. To validate transcriptional data, we also compared the immunohistochemical analysis of heterogeneous spheroids to melanoma biopsies. We have distinguished three functional clusters in primary human fibroblasts from melanoma spheroids. These clusters differed in the expression of (a) extracellular matrix-related genes, (b) pro-inflammatory factors, and (c) TGFβ signalling superfamily. We observed a broader deregulation of gene transcription in previously photodamaged cells. We have confirmed that pro-inflammatory cytokine IL-6 significantly enhances melanoma invasion to the extracellular matrix in our model. This supports the opinion that the aspects of ageing are essential for reliable melanoma 3D modelling in vitro.

• Klíčová slova
• Interleukin-6, cytokine, extracellular matrix, fibroblasts, heterogeneity, melanoma, senescence-associated secretory phenotype, single-cell sequencing, spheroids, subpopulation,
• Publikační typ
• časopisecké články MeSH

Similarly to other types of malignant tumours, the incidence of head and neck cancer is increasing globally. It is frequently associated with smoking and alcohol abuse, and in a broader sense also with prolonged exposure to these factors during ageing. A higher incidence of tumours observed in younger populations without a history of alcohol and tobacco abuse may be due to HPV infection. Malignant tumours form an intricate ecosystem of cancer cells, fibroblasts, blood/lymphatic capillaries and infiltrating immune cells. This dynamic system, the tumour microenvironment, has a significant impact on the biological properties of cancer cells. The microenvironment participates in the control of local aggressiveness of cancer cells, their growth, and their consequent migration to lymph nodes and distant organs during metastatic spread. In cancers originating from squamous epithelium, a similarity was demonstrated between the cancer microenvironment and healing wounds. In this review, we focus on the specificity of the microenvironment of head and neck cancer with emphasis on the mechanism of intercellular crosstalk manipulation for potential therapeutic application.

• Klíčová slova
• IL-6, cancer, cancer ecosystem, cancer microenvironment, cancer therapy, cancer-associated fibroblast, cytokine, extracellular matrix, tumour-associated macrophages,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH