Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME-mediated by cytokines such as IL-6, TGF-b, and galectins-further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME.

• Keywords
• CAF, IL-6, cancer, cancer-associated fibroblast, extracellular matrix, head and neck squamous cell carcinoma, immunity, stroma, therapy, tumour microenvironment,
• MeSH
• Squamous Cell Carcinoma of Head and Neck * immunology   pathology   MeSH
• Cancer-Associated Fibroblasts immunology   pathology   MeSH
• Papillomavirus Infections immunology   complications   MeSH
• Humans MeSH
• Neoplastic Stem Cells immunology   pathology   MeSH
• Tumor Microenvironment * immunology   MeSH
• Head and Neck Neoplasms * immunology   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

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.

• Keywords
• Cancer-associated fibroblasts, Ectomesenchyme, Expression pattern, Fibroblasts, Homeobox genes, Mesoderm,
• MeSH
• Adult MeSH
• Fibroblasts * metabolism   cytology   MeSH
• Genes, Homeobox * MeSH
• Homeodomain Proteins * genetics   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Mesoderm * metabolism   cytology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Homeodomain Proteins * 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.

• Keywords
• IL-6, cancer-associated fibroblasts, granulation tissue, myofibroblasts, wound healing,
• MeSH
• Autoimmunity * MeSH
• Wound Healing * immunology   MeSH
• Interleukin-6 * metabolism   immunology   MeSH
• Humans MeSH
• Tumor Microenvironment * immunology   MeSH
• Neoplasms * immunology   metabolism   pathology   MeSH
• Aging * immunology   MeSH
• Inflammation * immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• 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.

• Keywords
• Xenopus laevis, RICs, ROCs, Regeneration,
• MeSH
• Single-Cell Analysis MeSH
• Extracellular Matrix metabolism   MeSH
• Wound Healing MeSH
• Tail * MeSH
• Regeneration * MeSH
• Transcriptome MeSH
• Xenopus laevis * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‑associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‑expression of keratins‑8/‑14 in the EM‑G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‑8, ‑14, ‑18, ‑19) and epithelial‑mesenchymal transition‑associated markers (SLUG, SNAIL, ZEB1, E‑/N‑cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‑A and MFGE8 attenuated the modulatory effect of CAFs on EM‑G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‑G3 cells in vitro. CAFs of different origins support the pro‑inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.

• Keywords
• breast cancer, cell differentiation, epithelial‑mesenchymal interaction, neutralizing antibody, tumor microenvironment,
• MeSH
• Antigens, Surface MeSH
• Cancer-Associated Fibroblasts * metabolism   MeSH
• Fibroblasts metabolism   MeSH
• Keratins genetics   metabolism   MeSH
• Humans MeSH
• Melanoma, Cutaneous Malignant MeSH
• MCF-7 Cells MeSH
• Milk Proteins genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Tumor Microenvironment genetics   MeSH
• Breast Neoplasms * drug therapy   genetics   metabolism   MeSH
• Prognosis MeSH
• Transcriptome MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antigens, Surface MeSH
• Keratins MeSH
• MFGE8 protein, human MeSH Browser
• Milk Proteins MeSH

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.

• Keywords
• IL-6, cancer-associated fibroblast, hypoxia, miR-21, miR-210, miRNA, pancreas,
• MeSH
• Diabetes Mellitus MeSH
• Carcinoma, Pancreatic Ductal * pathology   MeSH
• Facies MeSH
• Cancer-Associated Fibroblasts * metabolism   MeSH
• Humans MeSH
• MicroRNAs * genetics   MeSH
• Cerebellum abnormalities   MeSH
• Cell Line, Tumor MeSH
• Pancreatic Neoplasms * pathology   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Fetal Growth Retardation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• MicroRNAs * MeSH
• MIRN217 microRNA, human MeSH Browser

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.

• Keywords
• IL-6, cancer, metastasis,
• MeSH
• Interleukin-6 metabolism   MeSH
• Humans MeSH
• Neoplasms * drug therapy   MeSH
• Antineoplastic Agents * therapeutic use   MeSH
• Signal Transduction MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH
• Antineoplastic Agents * 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.

• Keywords
• IL-6, cancer ecosystem, cancer microenvironment, cancer-associated fibroblast, exosome,
• MeSH
• Exosomes metabolism   MeSH
• Cancer-Associated Fibroblasts metabolism   MeSH
• Interleukin-6 metabolism   MeSH
• Humans MeSH
• Tumor Microenvironment MeSH
• Neoplasms metabolism   MeSH
• Paracrine Communication MeSH
• Cell Movement MeSH
• Cell Proliferation MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH