Cancer-associated fibroblasts (CAFs) represent an important component of the cancer ecosystem, influencing the broad scale of biological properties of tumour cells, including the capacity for metastasis formation. An important CAF subpopulation, known as myCAFs, typically expresses α-smooth muscle actin. Transcriptomic analysis demonstrated that activated fibroblasts isolated from various pathological tissues also express the ACTG2 gene encoding γ-smooth muscle actin. This was further validated by immunocytochemistry. Using the scratch test in vitro, it was possible to demonstrate that γ-smooth muscle actin may be associated with the epithelial-mesenchymal transition, which was also shown by transcriptomic analysis. The presence of γ-smooth muscle actin-positive fibroblasts in histopathological sections of human tumours verified the expression of this protein as a new potential marker of CAFs.

• Klíčová slova
• CLEC12A, TPD52L1, Cancer-associated fibroblast, Epithelial-mesenchymal transition, γ-smooth muscle actin,
• MeSH
• aktiny * metabolismus   genetika   analýza   MeSH
• fibroblasty asociované s nádorem * metabolismus   patologie   MeSH
• lidé MeSH
• nádorové biomarkery * metabolismus   genetika   analýza   MeSH
• nádory * patologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ACTA2 protein, human MeSH Prohlížeč
• aktiny * MeSH
• nádorové biomarkery * MeSH

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.

• Klíčová slova
• CAF, IL-6, cancer, cancer-associated fibroblast, extracellular matrix, head and neck squamous cell carcinoma, immunity, stroma, therapy, tumour microenvironment,
• MeSH
• dlaždicobuněčné karcinomy hlavy a krku * imunologie   patologie   MeSH
• fibroblasty asociované s nádorem imunologie   patologie   MeSH
• infekce papilomavirem imunologie   komplikace   MeSH
• lidé MeSH
• nádorové kmenové buňky imunologie   patologie   MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory hlavy a krku * imunologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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.

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

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

• Klíčová slova
• IL-6, cancer microenvironment, head and neck cancer, targeted therapy,
• MeSH
• interleukin-6 imunologie   metabolismus   MeSH
• lidé MeSH
• nádorové mikroprostředí * MeSH
• nádory hlavy a krku imunologie   terapie   MeSH
• signální transdukce MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• interleukin-6 MeSH

Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different "sensitizing ratio". Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.

• Klíčová slova
• cancer recurrence, cancer-associated fibroblasts, cisplatin, coculture, head and neck cancer, patient-derived cell cultures, treatment resistance,
• MeSH
• chemorezistence účinky léků   MeSH
• cisplatina farmakologie   MeSH
• dlaždicobuněčné karcinomy hlavy a krku metabolismus   patologie   MeSH
• fibroblasty asociované s nádorem účinky léků   metabolismus   MeSH
• kokultivační techniky MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru metabolismus   patologie   MeSH
• nádorové buněčné linie MeSH
• nádory hlavy a krku metabolismus   patologie   MeSH
• parakrinní signalizace účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• testy nádorových kmenových buněk MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cisplatina MeSH
• protinádorové látky MeSH

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

• Klíčová slova
• cancer, cytokine, galectin, stem cell, tissue repair,
• MeSH
• buněčné mikroprostředí MeSH
• cytokiny metabolismus   MeSH
• galektiny metabolismus   MeSH
• hojení ran MeSH
• imunitní systém cytologie   imunologie   metabolismus   MeSH
• keloid metabolismus   patologie   MeSH
• lidé MeSH
• mezibuněčné signální peptidy a proteiny metabolismus   MeSH
• nádorové kmenové buňky metabolismus   patologie   MeSH
• nádorové mikroprostředí * MeSH
• nádory imunologie   metabolismus   patologie   MeSH
• rány a poranění imunologie   metabolismus   patologie   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• galektiny MeSH
• mezibuněčné signální peptidy a proteiny MeSH

Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle-also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.

• Klíčová slova
• cancer microenvironment, cancer-associated fibroblast, niche, stem cell, wound healing,
• MeSH
• epidermální buňky MeSH
• epitelové buňky patologie   MeSH
• fibroblasty patologie   MeSH
• hojení ran fyziologie   MeSH
• keratinocyty patologie   MeSH
• lidé MeSH
• melanom patologie   MeSH
• mezenchymální kmenové buňky patologie   MeSH
• nádorové kmenové buňky patologie   MeSH
• nádorové mikroprostředí fyziologie   MeSH
• nádory kůže patologie   MeSH
• nika kmenových buněk fyziologie   MeSH
• vlasový folikul cytologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Cancer-associated fibroblasts are bioactive elements influencing the biological properties of malignant tumors. Their origin from different cell types has been established, and the possibility of their formation by epithelial-to-mesenchymal transition from cancer cells is under debate. This study shows that human cancer cells grafted to nu/nu mice induced formation of tumor stroma with the presence of typical smooth muscle actin-containing cancer-associated fibroblasts. These cells seem to be of the host origin because they are not recognized by an antibody specific for human vimentin, as was also verified in vitro. These results suggest that cancer-associated stromal fibroblasts are not formed by epithelial-to-mesenchymal transition from cancer cells.

• MeSH
• adenokarcinom metabolismus   patologie   MeSH
• buněčný rodokmen * MeSH
• buňky HT-29 MeSH
• buňky stromatu metabolismus   patologie   MeSH
• časové faktory MeSH
• dlaždicobuněčné karcinomy hlavy a krku MeSH
• epitelo-mezenchymální tranzice * MeSH
• fibroblasty metabolismus   patologie   MeSH
• heterografty MeSH
• kolorektální nádory metabolismus   patologie   MeSH
• lidé MeSH
• myši nahé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory hlavy a krku metabolismus   patologie   MeSH
• nádory hltanu metabolismus   patologie   MeSH
• spinocelulární karcinom metabolismus   patologie   MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH

BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.

• MeSH
• buněčná diferenciace * genetika   MeSH
• chemokin CXCL1 farmakologie   MeSH
• dospělí MeSH
• epidermální buňky * MeSH
• epidermis patologie   MeSH
• fibroblastový růstový faktor 2 farmakologie   MeSH
• interleukin-8 farmakologie   MeSH
• keratin-10 metabolismus   MeSH
• keratin-14 metabolismus   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanocyty metabolismus   MeSH
• melanom metabolismus   patologie   MeSH
• metastázy nádorů MeSH
• mezibuněčná komunikace * MeSH
• nádorové buněčné linie MeSH
• proteiny S100 metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CXCL1 MeSH
• fibroblastový růstový faktor 2 MeSH
• interleukin-8 MeSH
• keratin-10 MeSH
• keratin-14 MeSH
• proteiny S100 MeSH
• vaskulární endoteliální růstový faktor A MeSH

It is widely recognized that stromal fibroblasts significantly influence biological properties of multiple tumors including breast cancer. However, these epithelial-mesenchymal interactions seem to be essential in tumor biology and it is not fully clear whether this interaction is tumor type-specific or has a more general non-specific character. To elucidate this question, we tested the effect of cancer-associated fibroblasts (CAFs) isolated from different types of tumors (breast cancer skin metastasis, cutaneous basal cell carcinoma and melanoma, squamous cell carcinoma arising from oral cavity mucous membrane) on the EM-G3 breast cancer cell line. The results were compared with control experiments using normal human dermal fibroblasts, 3T3 mouse fibroblasts, and 3T3 fibroblasts influenced by the fibroblasts prepared from the basal cell carcinoma. Our results demonstrated that expression of luminal marker keratin 8 was influenced only by CAFs prepared from any tested tumors. In contrast, all tested types of fibroblasts showed a strong stimulatory effect on the expression of basal/myoepithelial marker keratin 14. The CAFs also elevated the number of cells with positivity for both keratins 8 and 14 that are similar to ductal originated precursor cells. The expression of proliferation marker Ki67 was not influenced by any of the tested fibroblasts. In conclusion, our data indicate that CAFs are able to influence the phenotype of a breast cancer cell line and this effect is based on a tumor type-unspecific mechanism. Finally, a clear functional difference between normal and CAFs was demonstrated.

• MeSH
• bazocelulární karcinom metabolismus   patologie   MeSH
• buňky 3T3 MeSH
• fibroblasty metabolismus   MeSH
• keratin-8 metabolismus   MeSH
• kokultivační techniky MeSH
• lidé MeSH
• melanom metabolismus   patologie   MeSH
• myši MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory kůže metabolismus   patologie   sekundární   MeSH
• nádory prsu metabolismus   patologie   MeSH
• spinocelulární karcinom metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• keratin-8 MeSH
• KRT8 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH