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Medicine Aug 2021Over-expression of vitronectin (VN) is associated with tumorigenesis. The present study aimed to evaluate the prognostic value of VN expression in gastric cancer.The...
Over-expression of vitronectin (VN) is associated with tumorigenesis. The present study aimed to evaluate the prognostic value of VN expression in gastric cancer.The least absolute shrinkage and selection operator analysis was performed to screen the hub gene from The Cancer Genome Atlas gastric cancer patients with complete follow-up data, and 347 patients were finally included. Moreover, 102 patients were enrolled from the Affiliated Fuzhou First Hospital of Fujian Medical University. VN expression in paired gastric cancer and adjacent gastric normal tissues was detected using immunohistochemistry, and the clinicopathological significance of VN expression was evaluated. The prognostic significance of VN expression in gastric cancer patients was evaluated using by Kaplan-Meier method and Cox regression analysis and confirmed using Oncomine.VN was the prognosis relative gene which screened by The Cancer Genome Atlas dataset. Moreover, we identified the VN expression in an external dataset by immunohistochemistry. The result demonstrated that VN expression was remarkedly elevated in gastric cancer tissues (P < .001). High VN expression correlated with higher pathological Tumor-Node-Metastasis stage, and poorer survival outcomes. Cox regression analysis showed that VN expression was independently predictive of overall survival (OS) and disease-free survival (P = .004, P < .001, respectively). A prognostic risk score for OS was built based on VN expression. A meta-analysis from Oncomine datasets revealed that significantly lower VN mRNA levels in gastric cancer correlated with poorer OS.VN expression could be a prognostic marker of gastric cancer.
Topics: Biomarkers, Tumor; Chi-Square Distribution; Humans; Kaplan-Meier Estimate; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Stomach Neoplasms; Vitronectin
PubMed: 34397822
DOI: 10.1097/MD.0000000000026766 -
Journal of Radiation Research May 2015Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse...
Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins.
Topics: Carbon; Cell Adhesion; Cell Adhesion Molecules; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Radiation; Extracellular Matrix Proteins; Heavy Ions; Humans; Matrix Metalloproteinase 9; Medulloblastoma; Photons; Radiation Dosage; Receptors, Vitronectin
PubMed: 25736470
DOI: 10.1093/jrr/rru120 -
Acta Biomaterialia Sep 2018Extracellular matrix (ECM) proteins are key mediators of cell/material interactions. The surface density and conformation of these proteins adsorbed on the material...
UNLABELLED
Extracellular matrix (ECM) proteins are key mediators of cell/material interactions. The surface density and conformation of these proteins adsorbed on the material surface influence cell adhesion and the cellular response. We have previously shown that subtle variations in surface chemistry lead to drastic changes in the conformation of adsorbed fibronectin (FN). On poly(ethyl acrylate) (PEA), FN unfolds and displays domains for cell adhesion and FN-FN interaction, whereas on poly(methyl acrylate) (PMA) - with only one methyl group less - FN remains globular as it is in solution. The effect of the strength of the protein/material interaction in cell response, and its relation to protein density and conformation, has received limited attention so far. In this work, we used FN-functionalized AFM cantilevers to evaluate, via force spectroscopy, the strength of interaction between fibronectin and the underlying polymer which controls FN conformation (PEA and PMA). We found that the strength of FN/PEA interaction is significantly higher than FN/PMA, which limits the mobility of FN layer on PEA, reduces the ability of cells to mechanically reorganize FN and then leads to enhanced proteolysis and degradation of the surrounding matrix with compromised cell viability. By contrast, both PEA and PMA support cell adhesion when FN density is increased and also in the presence of serum or other serum proteins, including vitronectin (VN) and bovine serum albumin (BSA), which provide a higher degree of mobility to the matrix.
STATEMENT OF SIGNIFICANCE
The identification of parameters influencing cell response is of paramount importance for the design of biomaterials that will act as synthetic scaffolds for cells to anchor, grow and, eventually, become specialised tissues. Cells interact with materials through an intermediate layer of proteins adsorbed on the material surface. It is known that the density and conformation of these proteins determine cell behaviour. Here we show that the strength of protein/material interactions, which has received very limited attention so far, is key to understand the cellular response to biomaterials. Very strong protein/material interactions reduce the ability of cells to mechanically reorganize proteins at the material interface which results in enhanced matrix degradation, leading ultimately to compromised cell viability.
Topics: 3T3 Cells; Acrylic Resins; Adsorption; Animals; Biocompatible Materials; Cell Adhesion; Cell Differentiation; Cell Lineage; Cell Survival; Extracellular Matrix; Fibronectins; Humans; Mice; Microscopy, Atomic Force; Microscopy, Fluorescence; Serum Albumin, Bovine; Surface Properties; Vitronectin
PubMed: 30006313
DOI: 10.1016/j.actbio.2018.07.016 -
Investigative Ophthalmology & Visual... Dec 2020Vitronectin, a cell adhesion and spreading factor, is suspected to play a role in the pathogenesis of age-related macular degeneration (AMD), as it is a major component...
PURPOSE
Vitronectin, a cell adhesion and spreading factor, is suspected to play a role in the pathogenesis of age-related macular degeneration (AMD), as it is a major component of AMD-specific extracellular deposits (e.g., soft drusen, subretinal drusenoid deposits). The present study addressed the impact of AMD-associated non-synonymous variant rs704 in the vitronectin-encoding gene VTN on vitronectin functionality.
METHODS
Effects of rs704 on vitronectin expression and processing were analyzed by semi-quantitative sequencing of VTN transcripts from retinal pigment epithelium (RPE) cells generated from human induced pluripotent stem cells (hiPSCs) and from human neural retina, as well as by western blot analyses on heterologously expressed vitronectin isoforms. Binding of vitronectin isoforms to retinal and endothelial cells was analyzed by western blot. Immunofluorescence staining followed extracellular matrix (ECM) deposition in cultured RPE cells heterologously expressing the vitronectin isoforms. Adhesion of fluorescently labeled RPE or endothelial cells in dependence of recombinant vitronectin or vitronectin-containing ECM was investigated fluorometrically or microscopically. Tube formation and migration assays addressed effects of vitronectin on angiogenesis-related processes.
RESULTS
Variant rs704 affected expression, secretion, and processing but not oligomerization of vitronectin. Cell binding and influence on RPE-mediated ECM deposition differed between AMD-risk-associated and non-AMD-risk-associated protein isoforms. Finally, vitronectin affected adhesion and endothelial tube formation.
CONCLUSIONS
The AMD-risk-associated vitronectin isoform exhibits increased expression and altered functionality in cellular processes related to the sub-RPE aspects of AMD pathology. Although further research is required to address the subretinal disease aspects, this initial study supports an involvement of vitronectin in AMD pathogenesis.
Topics: Blotting, Western; Cell Encapsulation; Cloning, Molecular; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix; Fluorescent Antibody Technique; Genetic Variation; Human Umbilical Vein Endothelial Cells; Humans; Macular Degeneration; Protein Isoforms; Recombinant Proteins; Retina; Retinal Pigment Epithelium; Vitronectin
PubMed: 33259607
DOI: 10.1167/iovs.61.14.2 -
Yakugaku Zasshi : Journal of the... 2020Viruses are natural nanocarriers that deliver various biological cargos, such as DNA, RNA, and proteins. We are developing a new nanocarrier by mimicking the early... (Review)
Review
Viruses are natural nanocarriers that deliver various biological cargos, such as DNA, RNA, and proteins. We are developing a new nanocarrier by mimicking the early mechanism of infection by hepatitis B virus (HBV). When the HBV envelope L protein is overexpressed in yeast cells, hollow nanoparticles displaying L proteins are synthesized. This nanoparticle, namely a bio-nanocapsule (BNC), can specifically attach to, and then internalize into, human hepatic cells by implementing the early mechanism of infection by HBV. In this review, we outlined the cellular uptake mechanism of HBV/BNC linking to L protein function. The L protein contains several functional domains in the pre-S1 region, including the fusogenic domain and the heparin-binding domain. The fusogenic domain corresponding to the pre-S1(9-24) region is responsible for the low pH-dependent membrane fusion of BNC. The heparin-binding domain corresponding to the pre-S1(30-42) region has a strong affinity to heparin as compared to that of known heparin-binding peptides, such as vitronectin and gp120 in human immunodeficiency virus-1. This heparin-binding domain binds to heparan sulfate proteoglycan (HSPG) at the cell surface of human hepatic cells. These functional domains are present in any virus, thus, these viral envelope proteins are very useful in designing novel DDS nanocarriers.
Topics: Drug Carriers; Drug Design; Heparan Sulfate Proteoglycans; Heparin; Hepatitis B virus; Humans; Nanocapsules; Protein Binding; Protein Domains; Viral Envelope Proteins
PubMed: 32009036
DOI: 10.1248/yakushi.19-00187-2 -
Turkish Journal of Pharmaceutical... Aug 2017Extracellular matrix components, including vitronectin (VN), soluble epithelial-cadherin (sE-cadherin) and transforming growth factor-beta 1 (TGF-β1), play a key role...
OBJECTIVES
Extracellular matrix components, including vitronectin (VN), soluble epithelial-cadherin (sE-cadherin) and transforming growth factor-beta 1 (TGF-β1), play a key role in the invasion and metastasis of cancer. The objective of the study was to determine the clinical significance of serum levels of these molecules in patients with endometrial and ovarian cancers.
MATERIALS AND METHODS
Serum levels of VN, sE-cadherin and TGF-β1 in patients with endometrial (n=28) and ovarian cancers (n=40) and healthy controls (n=41) were measured by ELISA using commercial kits.
RESULTS
A significant difference was found in VN, sE-cadherin and TGF-β1 levels between patients and healthy controls (p<0.01, p<0.01 and p<0.05, respectively). Serum VN and sE-cadherin levels were decreased significantly in both endometrial and ovarian cancer patients compared to controls (p<0.01, p<0.01, respectively). Conversely, TGF-β1 levels were increased significantly in patients with ovarian cancer as compared to controls (p<0.01). There was no significant difference between healthy controls and endometrial cancer patients.
CONCLUSION
In conclusion, our study reveals that serum VN, sE-cadherin and TGF-β1 levels can be candidate targets for providing new diagnostic procedures in endometrial and ovarian cancers.
PubMed: 32454605
DOI: 10.4274/tjps.81994 -
Annals of Thoracic and Cardiovascular... Oct 2022Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of...
BACKGROUND
Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of hsa_circ_0079530 (circ_0079530) in NSCLC development and radiosensitivity are largely unknown.
METHODS
The abundances of circ_0079530, microRNA (miR-409-3p), aquaporin 4 (AQP4), E-cadherin, intercellular adhesion molecule-1, vitronectin, proliferating cell nuclear antigen, and matrix metalloproteinase 9 were determined via quantitative reverse transcription polymerase chain reaction or western blotting. Cell proliferation, survival fraction, cycle process, migration, invasion, and in vivo growth were examined by cell counting kit-8, colony formation, flow cytometry, transwell, and xenograft analyses. The binding relationship was assessed via dual-luciferase reporter assay and RNA immunoprecipitation assay.
RESULTS
Circ_0079530 expression was increased in NSCLC tissues and radioresistant samples. Circ_0079530 knockdown restrained cell proliferation, migration, and invasion, and facilitated radiosensitivity. Circ_0079530 silence decreased tumor growth with or without radiation treatment. Circ_0079530 was verified as a miR-409-3p sponge, and miR-409-3p downregulation mitigated the effects of circ_0079530 interference on NSCLC cell malignancy and radiosensitivity. AQP4 was directly targeted by miR-409-3p. MiR-409-3p restrained cell proliferation, migration, and invasion, and enhanced radiosensitivity by decreasing AQP4 expression. Notably, circ_0079530 silence decreased AQP4 expression by regulating miR-409-3p expression.
CONCLUSION
Circ_0079530 silence repressed cell proliferation, migration, and invasion, and facilitated radiosensitivity in NSCLC cells by mediating miR-409-3p/AQP4 axis.
Topics: Humans; Aquaporin 4; Cadherins; Carcinoma, Non-Small-Cell Lung; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Intercellular Adhesion Molecule-1; Lung Neoplasms; Matrix Metalloproteinase 9; MicroRNAs; Proliferating Cell Nuclear Antigen; Radiation Tolerance; RNA, Circular; Treatment Outcome; Vitronectin
PubMed: 35896371
DOI: 10.5761/atcs.oa.21-00237 -
Andrology Mar 2022To investigate the effect of icariin on endothelial microparticles, endothelial progenitor cells, platelets, and erectile function in spontaneously hypertensive rats.
OBJECTIVES
To investigate the effect of icariin on endothelial microparticles, endothelial progenitor cells, platelets, and erectile function in spontaneously hypertensive rats.
MATERIALS AND METHODS
Twelve 8-week-old healthy male Wistar-Kyoto rats and 12 spontaneously hypertensive rats were randomly divided into four following groups: Wistar-Kyoto control group (normal saline 1 ml/d given by gavage), Wistar-Kyoto + icariin group (icariin 10 mg/kg × d dissolved in 1 ml normal saline and given by gavage), spontaneously hypertensive rats control group (normal saline 1 ml/d given by gavage), and spontaneously hypertensive rats + icariin group (icariin 10 mg/kg × d dissolved in 1 ml normal saline and given by gavage). Four weeks later, the maximum intracavernous pressure/mean arterial pressure, platelet count, mean platelet volume, platelet distribution width, endothelial microparticles, endothelial progenitor cells, and vitronectin receptor were measured in each group.
RESULTS
Under 3 or 5 V electrical stimulation, the maximum intracavernous pressure/mean arterial pressure in the spontaneously hypertensive rats + icariin group (0.23 ± 0.03, 0.38 ± 0.02) was significantly higher compared to the spontaneously hypertensive rats control group (0.12 ± 0.02, 0.20 ± 0.02) (p<0.05). Platelet count, mean platelet volume, and platelet distribution width in the spontaneously hypertensive rats + icariin group (1103.67 ± 107.70 × 10 /L, 9.08 ± 0.50 fl, 11.87 ± 0.45%) were significantly lower than those in the spontaneously hypertensive rats control group (1298.00 ± 89.54 × 10 /L, 9.72 ± 0.44 fl, 13.03 ± 0.59%) (all p < 0.05). Endothelial microparticles, endothelial progenitor cells, and vitronectin receptor in the spontaneously hypertensive rats + icariin group (1.01 ± 0.28%, 1.53 ± 0.65%, 2.13 ± 0.53%) were significantly lower than those in the spontaneously hypertensive rats control group (1.58 ± 0.19%, 2.71 ± 0.64%, 3.76 ± 0.52%) (all p < 0.05). Moreover, maximum intracavernous pressure/mean arterial pressure was strongly negatively correlated with platelet distribution width and vitronectin receptor (r > 0.7), and maximum intracavernous pressure/mean arterial pressure was moderately negatively correlated with mean platelet volume, endothelial microparticles, and endothelial progenitor cells (0.5 < r<0.7).
CONCLUSION
Icariin may improve erectile function in spontaneously hypertensive rats by reducing the content of endothelial microparticles in blood and inhibiting the activation of the platelets. Endothelial microparticles, endothelial progenitor cells, and platelet activation-related (mean platelet volume, platelet distribution width, and vitronectin receptor) can be used as indicators for icariin to improve erectile function in spontaneously hypertensive rats.
Topics: Animals; Blood Platelets; Endothelial Progenitor Cells; Erectile Dysfunction; Flavonoids; Humans; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY
PubMed: 34779135
DOI: 10.1111/andr.13127 -
BMC Cancer Nov 2018microRNAs (miRNAs) stably exist in circulating blood and are encapsulated in extracellular vesicles such as exosomes. The aims of this study were to identify which...
Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells.
BACKGROUND
microRNAs (miRNAs) stably exist in circulating blood and are encapsulated in extracellular vesicles such as exosomes. The aims of this study were to identify which exosomal miRNAs are highly produced from epithelial ovarian cancer (EOC) cells, to analyze whether serum miRNA can be used to discriminate patients with EOC from healthy volunteers, and to investigate the functional role of exosomal miRNAs in ovarian cancer progression.
METHODS
Exosomes were collected from the culture media of serous ovarian cancer cell lines, namely TYK-nu and HeyA8 cells. An exosomal miRNA microarray revealed that several miRNAs including miR-99a-5p were specifically elevated in EOC-derived exosomes. Expression levels of serum miR-99a-5p in 62 patients with EOC, 26 patients with benign ovarian tumors, and 20 healthy volunteers were determined by miRNA quantitative reverse transcription-polymerase chain reaction. To investigate the role of exosomal miR-99a-5p in peritoneal dissemination, neighboring human peritoneal mesothelial cells (HPMCs) were treated with EOC-derived exosomes and then expression levels of miR-99a-5p were examined. Furthermore, mimics of miR-99a-5p were transfected into HPMCs and the effect of miR-99a-5p on cancer invasion was analyzed using a 3D culture model. Proteomic analysis with the tandem mass tag method was performed on HPMCs transfected with miR-99a-5p and then potential target genes of miR-99a-5p were examined.
RESULTS
The serum miR-99a-5p levels were significantly increased in patients with EOC, compared with those in benign tumor patients and healthy volunteers (1.7-fold and 2.8-fold, respectively). A receiver operating characteristic curve analysis showed with a cut-off of 1.41 showed sensitivity and specificity of 0.85 and 0.75, respectively, for detecting EOC (area under the curve = 0.88). Serum miR-99a-5p expression levels were significantly decreased after EOC surgeries (1.8 to 1.3, p = 0.002), indicating that miR-99a-5p reflects tumor burden. Treatment with EOC-derived exosomes significantly increased miR-99a-5p expression in HPMCs. HPMCs transfected with miR-99a-5p promoted ovarian cancer invasion and exhibited increased expression levels of fibronectin and vitronectin.
CONCLUSIONS
Serum miR-99a-5p is significantly elevated in ovarian cancer patients. Exosomal miR-99a-5p from EOC cells promotes cell invasion by affecting HPMCs through fibronectin and vitronectin upregulation and may serve as a target for inhibiting ovarian cancer progression.
Topics: Adult; Aged; Cell Line, Tumor; Epithelium; Exosomes; Female; Fibronectins; Gene Expression Regulation, Neoplastic; Healthy Volunteers; Humans; MicroRNAs; Middle Aged; Neoplasm Invasiveness; Neoplasms; Ovarian Neoplasms; Peritoneum; Vitronectin
PubMed: 30396333
DOI: 10.1186/s12885-018-4974-5 -
BMC Microbiology Oct 2015Candida parapsilosis and C. tropicalis increasingly compete with C. albicans-the most common fungal pathogen in humans-as causative agents of severe candidiasis in...
BACKGROUND
Candida parapsilosis and C. tropicalis increasingly compete with C. albicans-the most common fungal pathogen in humans-as causative agents of severe candidiasis in immunocompromised patients. In contrast to C. albicans, the pathogenic mechanisms of these two non-albicans Candida species are poorly understood. Adhesion of Candida yeast to host cells and the extracellular matrix is critical for fungal invasion of hosts.
METHODS
The fungal proteins involved in interactions with extracellular matrix proteins were isolated from mixtures of β-1,3-glucanase- or β-1,6-glucanase-extractable cell wall-associated proteins by use of affinity chromatography and chemical cross-linking methods, and were further identified by liquid chromatography-coupled tandem mass spectrometry.
RESULTS
In the present study, we characterized the binding of three major extracellular matrix proteins--fibronectin, vitronectin and laminin--to C. parapsilosis and C. tropicalis pseudohyphae. The major individual compounds of the fungal cell wall that bound fibronectin, vitronectin and laminin were found to comprise two groups: (1) true cell wall components similar to C. albicans adhesins from the Als, Hwp and Iff/Hyr families; and (2) atypical (cytoplasm-derived) surface-exposed proteins, including malate synthase, glucose-6-phosphate isomerase, 6-phosphogluconate dehydrogenase, enolase, fructose-1,6-bisphosphatase, transketolase, transaldolase and elongation factor 2.
DISCUSSION
The adhesive abilities of two investigated non-albicans Candida species toward extracellular matrix proteins were comparable to those of C. albicans suggesting an important role of this particular virulence attribute in the pathogenesis of infections caused by C. tropicalis and C. parapsilosis.
CONCLUSIONS
Our results reveal new insight into host-pathogen interactions during infections by two important, recently emerging, fungal pathogens.
Topics: Candida; Cell Wall; Chromatography, Affinity; Chromatography, Liquid; Fibronectins; Fungal Proteins; Host-Pathogen Interactions; Humans; Laminin; Protein Binding; Protein Interaction Mapping; Tandem Mass Spectrometry; Vitronectin
PubMed: 26438063
DOI: 10.1186/s12866-015-0531-4