Nejvíce citovaný článek - PubMed ID 11533706
Air pollution is the leading cause of lung cancer after tobacco smoking, contributing to 20% of all lung cancer deaths. Increased risk associated with living near trafficked roads, occupational exposure to diesel exhaust, indoor coal combustion and cigarette smoking, suggest that combustion components in ambient fine particulate matter (PM2.5), such as polycyclic aromatic hydrocarbons (PAHs), may be central drivers of lung cancer. Activation of the aryl hydrocarbon receptor (AhR) induces expression of xenobiotic-metabolizing enzymes (XMEs) and increase PAH metabolism, formation of reactive metabolites, oxidative stress, DNA damage and mutagenesis. Lung cancer tissues from smokers and workers exposed to high combustion PM levels contain mutagenic signatures derived from PAHs. However, recent findings suggest that ambient air PM2.5 exposure primarily induces lung cancer development through tumor promotion of cells harboring naturally acquired oncogenic mutations, thus lacking typical PAH-induced mutations. On this background, we discuss the role of AhR and PAHs in lung cancer development caused by air pollution focusing on the tumor promoting properties including metabolism, immune system, cell proliferation and survival, tumor microenvironment, cell-to-cell communication, tumor growth and metastasis. We suggest that the dichotomy in lung cancer patterns observed between smoking and outdoor air PM2.5 represent the two ends of a dose-response continuum of combustion PM exposure, where tumor promotion in the peripheral lung appears to be the driving factor at the relatively low-dose exposures from ambient air PM2.5, whereas genotoxicity in the central airways becomes increasingly more important at the higher combustion PM levels encountered through smoking and occupational exposure.
- Klíčová slova
- Air pollution, Carcinogenesis, Diesel exhaust, Genotoxicity, Inflammation, Occupational exposure, Smoking, Tumor metastasis, Tumor microenvironment, Tumor promotion,
- MeSH
- látky znečišťující vzduch * toxicita MeSH
- lidé MeSH
- monitorování životního prostředí MeSH
- nádorové mikroprostředí MeSH
- nádory plic * chemicky indukované genetika MeSH
- pevné částice toxicita MeSH
- polycyklické aromatické uhlovodíky * toxicita MeSH
- receptory aromatických uhlovodíků genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- látky znečišťující vzduch * MeSH
- pevné částice MeSH
- polycyklické aromatické uhlovodíky * MeSH
- receptory aromatických uhlovodíků MeSH
The presence of key hypoxia regulators, namely, hypoxia-inducible factor (HIF)-1α or HIF-2α, in tumors is associated with poor patient prognosis. Hypoxia massively activates several genes, including the one encoding the BCRP transporter that proffers multidrug resistance to cancer cells through the xenobiotic efflux and is a determinant of the side population (SP) associated with cancer stem-like phenotypes. As natural medicine comes to the fore, it is instinctive to look for natural agents possessing powerful features against cancer resistance. Hypericin, a pleiotropic agent found in Hypericum plants, is a good example as it is a BCRP substrate and potential inhibitor, and an SP and HIF modulator. Here, we showed that hypericin efficiently accumulated in hypoxic cancer cells, degraded HIF-1/2α, and decreased BCRP efflux together with hypoxia, thus diminishing the SP population. On the contrary, this seemingly favorable result was accompanied by the stimulated migration of this minor population that preserved the SP phenotype. Because hypoxia unexpectedly decreased the BCRP level and SP fraction, we compared the SP and non-SP proteomes and their changes under hypoxia in the A549 cell line. We identified differences among protein groups connected to the epithelial-mesenchymal transition, although major changes were related to hypoxia, as the upregulation of many proteins, including serpin E1, PLOD2 and LOXL2, that ultimately contribute to the initiation of the metastatic cascade was detected. Altogether, this study helps in clarifying the innate and hypoxia-triggered resistance of cancer cells and highlights the ambivalent role of natural agents in the biology of these cells.
- Klíčová slova
- Breast cancer resistance protein, ECM reorganization, Hypericin, Hypoxia, Proteomics, Side population,
- MeSH
- ABC transportér z rodiny G, člen 2 genetika metabolismus MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus MeSH
- hypoxie buňky MeSH
- hypoxie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny genetika metabolismus MeSH
- nádory * metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- vedlejší populace buněk * patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ABC transportér z rodiny G, člen 2 MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
- hypericin MeSH Prohlížeč
- nádorové proteiny MeSH
- transkripční faktory bHLH MeSH
These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
- MeSH
- DNA analýza MeSH
- falešně pozitivní reakce MeSH
- imunofenotypizace MeSH
- imunologické techniky * MeSH
- lidé MeSH
- proliferace buněk MeSH
- průtoková cytometrie MeSH
- řízení kvality MeSH
- RNA analýza MeSH
- separace buněk MeSH
- směrnice jako téma * MeSH
- software MeSH
- T-lymfocyty cytologie MeSH
- výzkumný projekt MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- DNA MeSH
- RNA MeSH
Malignant mesothelioma (MM) is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs) that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.
- MeSH
- antigen CD24 metabolismus MeSH
- buněčná adheze účinky léků MeSH
- buněčné sféroidy účinky léků patologie MeSH
- fenotyp MeSH
- genový knockdown MeSH
- inhibiční koncentrace 50 MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- maligní mezoteliom MeSH
- mezoteliom metabolismus patologie MeSH
- mitochondrie účinky léků metabolismus MeSH
- myši nahé MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky účinky léků metabolismus patologie MeSH
- nádory plic metabolismus patologie MeSH
- progrese nemoci MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie MeSH
- tokoferoly farmakologie MeSH
- transplantace nádorů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigen CD24 MeSH
- nádorové biomarkery MeSH
- protinádorové látky MeSH
- tokoferoly MeSH
