Microenvironment
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elektronický časopis
Nádorové mikroprostředí hraje esenciální roli v podpoře růstu, proliferace a schopnosti nádorových buněk zakládat metastatická ložiska. Je tvořeno převážně z nádorově asociovaných fibroblastů a jimi produkované extracelulární matrix, imunitních buněk (makrofágy, granulocyty, mastocyty a lymfocyty), cév, adipocytů a mezenchymových kmenových buněk. Tyto buňky se vzájemně ovlivňují, a to jak pomocí intercelulární komunikace, tak prostřednictvím signálních molekul. Mezi signální molekuly patří například růstové faktory, chemokiny, interleukiny nebo galektiny. V přehledovém článku prezentujeme současné poznatky o jednotlivých skupinách buněk a jejich vzájemné interakci. Prezentované informace jsou vztaženy zejména k již aplikovanému nebo v budoucnu perspektivnímu klinickému využití.
Cancer microenvironment plays an essential role in promoting the growth, proliferation and ability of cancer cells to establish metastatic deposits. This microenvironment consists predominantly of cancer-associated fibroblasts and the extracellular matrix produced by them, immune cells (macrophages, granulocytes, mast cells and lymphocytes), blood vessels, adipocytes and mesenchymal stem cells. These cells interact with each other, both via intercellular communication and signal molecules. The signal molecules include, for example, growth factors, chemokines, interleukins or galectins. In the review article, we present the current knowledge about individual cell groups and their interaction. The presented information relates mainly to the already applied or future prospective clinical use.
- Klíčová slova
- nádorově asociované fibroblasty, růstové faktory,
- MeSH
- chemokiny MeSH
- extracelulární matrix * MeSH
- galektiny MeSH
- interleukiny MeSH
- kmenové buňky MeSH
- lidé MeSH
- nádory hlavy a krku * etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and the effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely, alterations in the metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show the effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in a healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from the metabolism of other tissues. Findings from different tissues are, therefore, not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.
- MeSH
- aminokyseliny MeSH
- glykolýza MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nádorové mikroprostředí * MeSH
- nádory * MeSH
- Check Tag
- lidé MeSH
- 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.
- 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
BACKGROUND: Prostate cancer (PCa) is a malignancy with significant immunosuppressive properties and limited immune activation. This immunosuppression is linked to reduced cytotoxic T cell activity, impaired antigen presentation, and elevated levels of immunosuppressive cytokines and immune checkpoint molecules. Studies demonstrate that cytotoxic CD8+ T cell infiltration correlates with improved survival, while increased regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are associated with worse outcomes and therapeutic resistance. Th1 cells are beneficial, whereas Th17 cells, producing interleukin-17 (IL-17), contribute to tumor progression. Tumor-associated neutrophils (TANs) and immune checkpoint molecules, such as PD-1/PD-L1 and T cell immunoglobulin-3 (TIM-3) are also linked to advanced stages of PCa. Chemotherapy holds promise in converting the "cold" tumor microenvironment (TME) to a "hot" one by depleting immunosuppressive cells and enhancing tumor immunogenicity. SUMMARY: This comprehensive review examines the immune microenvironment in PCa, focusing on the intricate interactions between immune and tumor cells in the TME. It highlights how TAMs, Tregs, cytotoxic T cells, and other immune cell types contribute to tumor progression or suppression and how PCa's low immunogenicity complicates immunotherapy. KEY MESSAGES: The infiltration of cytotoxic CD8+ T cells and Th1 cells correlates with better outcomes, while elevated T regs and TAMs promote tumor growth, metastasis, and resistance. TANs and natural killer (NK) cells exhibit dual roles, with higher NK cell levels linked to better prognoses. Immune checkpoint molecules like PD-1, PD-L1, and TIM-3 are associated with advanced disease. Chemotherapy can improve tumor immunogenicity by depleting T regs and myeloid-derived suppressor cells, offering therapeutic promise.
- MeSH
- imunoterapie metody MeSH
- lidé MeSH
- makrofágy spojené s nádory imunologie MeSH
- nádorové mikroprostředí * imunologie MeSH
- nádory prostaty * imunologie patologie terapie MeSH
- regulační T-lymfocyty imunologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Colorectal cancer (CRC) is one of the most common cancers worldwide. The patient's prognosis largely depends on the tumor stage at diagnosis. The pathological TNM Classification of Malignant Tumors (pTNM) staging of surgically resected cancers represents the main prognostic factor and guidance for decision-making in CRC patients. However, this approach alone is insufficient as a prognostic predictor because clinical outcomes in patients at the same histological tumor stage can still differ. Recently, significant progress in the treatment of CRC has been made due to improvements in both chemotherapy and surgical management. Immunotherapy-based approaches are one of the most rapidly developing areas of tumor therapy. This review summarizes the current knowledge about the tumor microenvironment (TME), immune response and its interactions with CRC development, immunotherapy and prognosis.
- MeSH
- imunita MeSH
- imunoterapie MeSH
- kolorektální nádory * patologie MeSH
- lidé MeSH
- nádorové mikroprostředí * MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cancer represents an extremely complicated ecosystem where cancer cells communicate with non-cancer cells present in the tumour niche through intercellular contacts, paracrine production of bioactive factors and extracellular vesicles, such as exosomes [...].
- MeSH
- ekosystém MeSH
- exozómy * metabolismus MeSH
- extracelulární vezikuly * metabolismus MeSH
- lidé MeSH
- mezibuněčná komunikace MeSH
- nádorové mikroprostředí MeSH
- nádory * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Migration Stimulating Factor (MSF) is a 70 kDa truncated isoform of fibronectin (FN); its mRNA is generated from the FN gene by an unusual two-stage processing. Unlike full-length FN, MSF is not a matrix molecule but a soluble protein which displays cytokine-like activities not displayed by any other FN isoform due to steric hindrance. There are two isoforms of MSF; these are referred to as MSF+aa and MSF-aa, while the term MSF is used to include both.MSF was first identified as a motogen secreted by foetal and cancer-associated fibroblasts in tissue culture. It is also produced by sprouting (angiogenic) endothelial cells, tumour cells and activated macrophages. Keratinocytes and resting endothelial cells secrete inhibitors of MSF that have been identified as NGAL and IGFBP-7, respectively. MSF+aa and MSF-aa show distinct functionality in that only MSF+aa is inhibited by NGAL.MSF is present in 70-80% of all tumours examined, expressed by the tumour cells as well as by fibroblasts, endothelial cells and macrophages in the tumour microenvironment (TME). High MSF expression is associated with tumour progression and poor prognosis in all tumours examined, including breast carcinomas, non-small cell lung cancer (NSCLC), salivary gland tumours (SGT) and oral squamous cell carcinomas (OSCC). Epithelial and stromal MSF carry independent prognostic value. MSF is also expressed systemically in cancer patients, being detected in serum and produced by fibroblast from distal uninvolved skin. MSF-aa is the main isoform associated with cancer, whereas MSF+aa may be expressed by both normal and malignant tissues.The expression of MSF is not invariant; it may be switched on and off in a reversible manner, which requires precise interactions between soluble factors present in the TME and the extracellular matrix in contact with the cells. MSF expression in fibroblasts may be switched on by a transient exposure to several molecules, including TGFβ1 and MSF itself, indicating an auto-inductive capacity.Acting by both paracrine and autocrine mechanisms, MSF stimulates cell migration/invasion, induces angiogenesis and cell differentiation and alters the matrix and cellular composition of the TME. MSF is also a survival factor for sprouting endothelial cells. IGD tri- and tetra-peptides mimic the motogenic and angiogenic activities of MSF, with both molecules inhibiting AKT activity and requiring αvβ3 functionality. MSF is active at unprecedently low concentrations in a manner which is target cell specific. Thus, different bioactive motifs and extracellular matrix requirements apply to fibroblasts, endothelial cells and tumour cells. Unlike other motogenic and angiogenic factors, MSF does not affect cell proliferation but it stimulates tumour growth through its angiogenic effect and downstream mechanisms.The epithelial-stromal pattern of expression and range of bioactivities displayed puts MSF in the unique position of potentially promoting tumour progression from both the "seed" and the "soil" perspectives.
- MeSH
- cytokiny MeSH
- endoteliální buňky MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory plic * MeSH
- nemalobuněčný karcinom plic * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
V průběhu hojení dochází k četným interakcím mezi fibroblasty, keratinocyty a buňkami imunitního systému. Uvolňování cytokinů podporuje tvorbu granulační tkáně, která vyplňuje poraněné místo. V případě narušení regulace tohoto komplexního děje dojde ke vzniku chronické rány. Tento problém často vídáme např. u diabetiků. Granulační tkáň je velmi podobná stromatu solidních nádorů. Tato práce se věnuje paralelám mezi hojící se ránou a nádorem. Klade si za cíl přehledně popsat regulaci obou procesů. Nové poznatky v této oblasti by mohly přispět k objevení nových terapeutických možností u chronických ran i solidních nádorů.
Numerous interactions occur among fibroblasts, keratinocytes and immune cells during wound healing. The release of cytokines supports formation of granular tissue which then fills the wound. A chronic wound appears when this complex process is disrupted. We can see this problem in patients with diabetes. Granular tissue is very similar to the stroma of solid tumors. This work is focused on parallels between a healing wound and tumor. It aims to clearly describe the regulation of both processes. New knowledge in this field can contribute to revealing new therapeutic possibilities in chronic wounds and solid tumors.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku * patofyziologie MeSH
- hojení ran MeSH
- lidé MeSH
- nádorové mikroprostředí * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability to target solid tumors, penetrate the tumor microenvironment (TME), and act as efficient drug delivery platforms highlights their potential in nanomedicine. However, the complex and dynamic nature of the TME, characterized by metabolic heterogeneity, immune suppression, and drug resistance, poses significant challenges to effective cancer treatment. GBMs offer innovative solutions by enhancing tumor targeting, facilitating deep tissue penetration, and modulating metabolic pathways that contribute to tumor progression and immune evasion. Their functionalization with targeting ligands and biocompatible polymers improves their biosafety and specificity, while their ability to modulate immune cell interactions within the TME presents new opportunities for immunotherapy. Given the role of metabolic reprogramming in tumor survival and resistance, GBMs could be further exploited in metabolism-targeted therapies by disrupting glycolysis, mitochondrial respiration, and lipid metabolism to counteract the immunosuppressive effects of the TME. This review focuses on discussing research studies that design GBM nanocomposites with enhanced biodegradability, minimized toxicity, and improved efficacy in delivering therapeutic agents with the intention to reprogram the TME for effective anticancer therapy. Additionally, exploring the potential of GBM nanocomposites in combination with immunotherapies and metabolism-targeted treatments could lead to more effective and personalized cancer therapies. By addressing these challenges, GBMs could play a pivotal role in overcoming current limitations in cancer treatment and advancing precision oncology.
- MeSH
- grafit * chemie terapeutické užití MeSH
- imunoterapie metody MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- nádorové mikroprostředí * účinky léků MeSH
- nádory * farmakoterapie metabolismus MeSH
- nanokompozity * chemie terapeutické užití MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH