Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Bryukhovetskiy, Igor; Шевченко, В. Е.

doi:10.3892/ol.2016.4756

Cited by 34 publications

(25 citation statements)

References 80 publications

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“…The expression of CD248 and Sca-1 was negatively regulated, and the expression of ITGA8 was positively regulated by transforming growth factor (TGF)-β, which plays a critical role in the progression of fibrosis of IPF [15][16][17][18], suggesting that expression of CD248 and ITGA8 may be potentially changed in the pro-fibrotic state. However, like normal human lungs, the CD248 high ITGA8 low human fibroblast-like cells were localized in collagen fiberrich connective tissue, and CD248 low ITGA8 high human fibroblast-like cells were localized in elastic fiber-rich connective tissue (Fig.…”

Section: Discussionmentioning

confidence: 99%

CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes

et al. 2020

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Background: Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. Methods: We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). Results: Mouse lung fibroblasts were classified into Sca-1 high fibroblasts and Sca-1 low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1 high fibroblasts and Sca-1 low fibroblasts, respectively. In mouse lungs, Sca-1 high fibroblasts and Sca-1 low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248 high ITGA8 low fibroblast-like cells and CD248 low ITGA8 high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. Conclusion: CD248 high ITGA8 low fibroblast-like cells and CD248 low ITGA8 high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.

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Section: Discussionmentioning

confidence: 99%

CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes

et al. 2020

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“…As has been mentioned, the elements of TGF-β-signaling are considered to be potential targets for anti-tumor therapy [11][12][13][14][15][16]33]. In parallel, new approaches with the use of NSCs/NPCs are being developed for treatment of gliomas of brain [1][2][3][4][5][6][7][8].…”

Section: Resultsmentioning

confidence: 99%

Morphometric characteristics of TGF-β1-positive cells of fetal rat brain in vitro

Любич¹,

Lisianyi²,

Малышева³

et al. 2016

JCOT

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One of the directions of cell therapy being developed for brain gliomas is the use of the neurogenic stem and progenitor cells (NSCs/NPCs). There are data on the anti-tumor and immunomodulating properties of the NSCs/NPCs the mechanisms of which were not disclosed yet. One of the potential targets for tumor therapy is the transforming growth factor β (TGF-β1) which is thought to be one of the key molecules in the regulation of proliferation, differentiation and cell survival or apoptosis. In the view of available information about the possibility of TGF-β1 production by the mammalian multipotent NSCs/NPCs, the aim of this work was to study the TGF-β1-positive cells in the dynamics of cultivation of fetal brain neurogenic cells as a potential source of anti-tumor or immunomodulating effects of these cells.Material and methods. The fetal rat brain cells on 14th (E14) day of gestation were used as the source for cultivation in standard conditions (DМЕМ + 1 % fetal bovine serum) and studied on the 2nd and 37thday by morphometry and immunocytochemistry.Results. In the fetal rat brain cell cultures, the TGF-β1-positive cells made 22.04 ± 2.33 % and the nestin-positive cells made 49.16 ± 10.60 % of the total cells number. The morphometric parameters of TGF-β1-positive cells exceeded the corresponding values of negative cells (average values of cross-sectional areas of the cytoplasm, cross-sectional areas of the nucleus, nuclear-cytoplasmic ratio). During cultivation the relative amount of TGF-β1-positive cells was slightly decreased 15.27 ± 9.80 % (p = 0.7) and their sizes were increased. On the 37th day of cultivation the sizes of TGF-β1-positive and their nuclei were smaller in the comparison with the TGF-β1-negative cells.Conclusions. The presence of TGF-β1 expression by part of neurogenic cells of fetal rat brain (E14) in vitro was found, which persisted throughout cultivation (~5 weeks). Significant quantitative differences of morphometric parameters of TGF-β1-positive and negative cells were detected.

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“…This cytokine has been demonstrated to trigger EMT in certain cases of breast cancer ( 13 ), renal carcinoma ( 14 ), intestinal tumors ( 15 – 17 ), pancreatic cancer ( 18 ) and glioblastoma ( 19 ). Previous research ( 20 ) demonstrated that stimulation of U87 MG cell lines with TGF-β1 significantly increases the production of proteins associated with invasion, proliferation, migration, DNA regeneration, stemness, and resistance to drugs and radiation. The resulting pool of glioblastoma cells has a molecular phenotype that is very similar to that of CSCs ( 21 ).…”

Section: Introductionmentioning

confidence: 97%

“…The resulting pool of glioblastoma cells has a molecular phenotype that is very similar to that of CSCs ( 21 ). It was reported that in human glioblastoma tumor cells, only two signaling pathways (the integrin and focal adhesion pathways) are available for regulatory effects on gene expression processes in the CSC nucleus ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

et al. 2018

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The majority of modern treatment methods for malignant brain tumors are not sufficiently effective, with a median survival time varying between 9 and 14 months. Metastatic and invasive processes are the principal characteristics of malignant tumors. The most important pathogenic mechanism is epithelial-mesenchymal transition (EMT), which causes epithelial cells to become more mobile, and capable of invading the surrounding tissues and migrating to distant organs. Transforming growth factor-β1 (TGF-β1) serves a key role in EMT-inducing mechanisms. The current study presented the interaction between hematopoietic stem cells and glioblastoma cells stimulated by TGF-β1 in vitro. The materials for the study were hematopoietic progenitor cell antigen CD34+ hematopoietic stem cells (HSCs) and U87 glioblastoma cells. Cell culture methods, automated monitoring of cell-cell interactions, confocal laser microscopy, flow cytometry and electron microscopy were used. It was demonstrated that U87 cells have a complex communication system, including adhesive intercellular contacts, areas of interdigitation with dissolution of the cytoplasm, cell fusion, communication microtubes and microvesicles. TGF-β1 affected glioblastoma cells by modifying the cell shape and intensifying their exocrine function. HSCs migrated to glioblastoma cells, interacted with them and exchanged fluorescent tags. Stimulation of cancer cells with TGF-β1 weakened the ability of glioblastoma cells to attract HSCs and exchange a fluorescent tag. This process stimulated cancer cell proliferation, which is an indication of the ability of HSCs to ‘switch’ the proliferation and invasion processes in glioblastoma cells.

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Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Cited by 34 publications

References 80 publications

CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes

CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes

Morphometric characteristics of TGF-β1-positive cells of fetal rat brain in vitro

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

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