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.

• Klíčová slova
• breast cancer, cell differentiation, epithelial‑mesenchymal interaction, neutralizing antibody, tumor microenvironment,
• MeSH
• antigeny povrchové MeSH
• fibroblasty asociované s nádorem * metabolismus   MeSH
• fibroblasty metabolismus   MeSH
• keratiny genetika   metabolismus   MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• MFC-7 buňky MeSH
• mléčné bílkoviny genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí genetika   MeSH
• nádory prsu * farmakoterapie   genetika   metabolismus   MeSH
• prognóza MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny povrchové MeSH
• keratiny MeSH
• MFGE8 protein, human MeSH Prohlížeč
• mléčné bílkoviny 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

"All-in-one" multifunctional nanomaterials, which can be visualized simultaneously by several imaging techniques, are required for the efficient diagnosis and treatment of many serious diseases. This report addresses the design and synthesis of upconversion magnetic NaGdF4:Yb3+/Er3+(Tm3+) nanoparticles by an oleic acid-stabilized high-temperature coprecipitation of lanthanide precursors in octadec-1-ene. The nanoparticles, which emit visible or UV light under near-infrared (NIR) irradiation, were modified by in-house synthesized PEG-neridronate to facilitate their dispersibility and colloidal stability in water and bioanalytically relevant phosphate buffered saline (PBS). The cytotoxicity of the nanoparticles was determined using HeLa cells and human fibroblasts (HF). Subsequently, the particles were modified by Bolton-Hunter-neridronate and radiolabeled by 125I to monitor their biodistribution in mice using single-photon emission computed tomography (SPECT). The upconversion and the paramagnetic properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles were evaluated by photoluminescence, magnetic resonance (MR) relaxometry, and magnetic resonance imaging (MRI) with 1 T and 4.7 T preclinical scanners. MRI data were obtained on phantoms with different particle concentrations and during pilot long-time in vivo observations of a mouse model. The biological and physicochemical properties of the NaGdF4:Yb3+/Er3+(Tm3+)@PEG nanoparticles make them promising as a trimodal optical/MRI/SPECT bioimaging and theranostic nanoprobe for experimental medicine.

• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

The ability of horse chestnut extract (HCE) to induce contraction force in fibroblasts, a process with remarkable significance in skin repair, motivated us to evaluate its wound healing potential in a series of experiments. In the in vitro study of the ability of human dermal fibroblasts to form myofibroblast-like cells was evaluated at the protein level (Western blot and immunofluorescence). The in vivo study was conducted on male Sprague-Dawley rats with inflicted wounds (one open circular and one sutured incision) on their backs. Rats were topically treated with two tested HCE concentrations (0.1% and 1%) or sterile water. The control group remained untreated. The incisions were processed for wound tensile strength (TS) measurement whereas the open wounds were subjected to histological examination. On the in vitro level the HCE extract induced fibronectin-rich extracellular matrix formation, but did not induced α-smooth muscle actin (SMA) expression in dermal fibroblasts. The animal study revealed that HCE increased wound TS and improved collagen organization. In conclusion, the direct comparison of both basic wound models demonstrated that the healing was significantly increased following HCE, thus this extract may be found useful to improve healing of acute wounds. Nevertheless, the use of an experimental rat model warrants a direct extrapolation to the human clinical situation.

• Klíčová slova
• horse chestnut, phytotherapy, repair and regeneration, wound healing,
• MeSH
• Aesculus chemie   MeSH
• extracelulární matrix účinky léků   metabolismus   MeSH
• hojení ran účinky léků   MeSH
• krysa rodu Rattus MeSH
• molekulární struktura MeSH
• myofibroblasty účinky léků   metabolismus   MeSH
• pevnost v tahu MeSH
• regenerace MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• rostlinné extrakty 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

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

Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.

• Klíčová slova
• Cancer-associated fibroblast, Cytokine, Keratinocyte, Melanocyte, Melanoma cells, Melanoma ecosystem,
• MeSH
• časná detekce nádoru metody   MeSH
• crista neuralis cytologie   patologie   MeSH
• indoly terapeutické užití   MeSH
• keratinocyty MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• melanocyty patologie   MeSH
• melanom farmakoterapie   epidemiologie   patologie   MeSH
• nádorové mikroprostředí fyziologie   MeSH
• nádory kůže MeSH
• protinádorové látky terapeutické užití   MeSH
• sulfonamidy terapeutické užití   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• vemurafenib MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• indoly MeSH
• protinádorové látky MeSH
• sulfonamidy MeSH
• vemurafenib MeSH

Clinical evidence suggests that healing is faster and almost scarless at an early neonatal age in comparison with that in adults. In this study, the phenotypes of neonatal and adult dermal fibroblasts and keratinocytes (nestin, smooth muscle actin, keratin types 8, 14 and 19, and fibronectin) were compared. Furthermore, functional assays (proliferation, migration, scratch wound closure) including mutual epithelial‑mesenchymal interactions were also performed to complete the series of experiments. Positivity for nestin and α smooth muscle actin was higher in neonatal fibroblasts (NFs) when compared with their adult counterparts (adult fibroblasts; AFs). Although the proliferation of NFs and AFs was similar, they significantly differed in their migration potential. The keratinocyte experiments revealed small, poorly differentiated cells (positive for keratins 8, 14 and 19) in primary cultures isolated from neonatal tissues. Moreover, the neonatal keratinocytes exhibited significantly faster rates of healing the experimentally induced in vitro defects in comparison with adult cells. Notably, the epithelial/mesenchymal interaction studies showed that NFs in co-culture with adult keratinocytes significantly stimulated the adult epithelial cells to acquire the phenotype of small, non-confluent cells expressing markers of poor differentiation. These results indicate the important differences between neonatal and adult cells that may be associated with improved wound healing during the early neonatal period.

• MeSH
• aktiny metabolismus   MeSH
• buněčná diferenciace MeSH
• crista neuralis cytologie   MeSH
• dárci tkání * MeSH
• dospělí MeSH
• epitelové buňky cytologie   metabolismus   MeSH
• fenotyp MeSH
• fibroblasty cytologie   metabolismus   MeSH
• fibronektiny biosyntéza   MeSH
• imunohistochemie MeSH
• keratinocyty cytologie   metabolismus   MeSH
• kmenové buňky metabolismus   MeSH
• kokultivační techniky MeSH
• lidé MeSH
• mezoderm cytologie   MeSH
• myofibroblasty cytologie   MeSH
• nestin metabolismus   MeSH
• neuroplasticita MeSH
• novorozenec MeSH
• pohyb buněk MeSH
• proliferace buněk MeSH
• stanovení celkové genové exprese MeSH
• stárnutí fyziologie   MeSH
• vývojová regulace genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ACTA2 protein, human MeSH Prohlížeč
• aktiny MeSH
• fibronektiny MeSH
• nestin 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