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Urinary Proteomics for Discovery of Gastric Cancer Biomarkers to Enable Precision Clinical Oncology.Omics : a Journal of Integrative Biology Aug 2023For precision in clinical oncology practice, detection of tumor-derived peptides and proteins in urine offers an attractive and noninvasive alternative for diagnostic or...
For precision in clinical oncology practice, detection of tumor-derived peptides and proteins in urine offers an attractive and noninvasive alternative for diagnostic or screening purposes. In this study, we report comparative quantitative proteomic profiling of urine samples from patients with gastric cancer and healthy controls using tandem mass tags-based multiplexed mass spectrometry approach. We identified 1504 proteins, of which 246 were differentially expressed in gastric cancer cases. Notably, ephrin A1 (EFNA1), pepsinogen A3 (PGA3), sortilin 1 (SORT1), and vitronectin (VTN) were among the upregulated proteins, which are known to play crucial roles in the progression of gastric cancer. We also found other overexpressed proteins, including shisa family member 5 (SHISA5), mucin like 1 (MUCL1), and leukocyte cell derived chemotaxin 2 (LECT2), which had not previously been linked to gastric cancer. Using a novel approach for targeted proteomics, SureQuant, we validated changes in abundance of a subset of proteins discovered in this study. We confirmed the overexpression of vitronectin and sortilin 1 in an independent set of urine samples. Altogether, this study provides molecular candidates for biomarker development in gastric cancer, and the findings also support the promise of urinary proteomics for noninvasive diagnostics and personalized/precision medicine in the oncology clinic.
Topics: Humans; Biomarkers, Tumor; Stomach Neoplasms; Proteomics; Vitronectin; Proteins; Medical Oncology; Biomarkers; Mucins; Intercellular Signaling Peptides and Proteins
PubMed: 37579183
DOI: 10.1089/omi.2023.0077 -
PloS One 2020Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early...
Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection. Vitronectin, a glycoprotein that is abundantly found in serum, extracellular matrix, and bone, binds to integrin αvβ3, and promotes cell adhesion and migration. Current studies indicate that patients with amplified vitronectin levels have lower survival rates than patients without amplified vitronectin levels. In this study, we focused on the role of vitronectin in breast cancer survival and its functional role as a non-invasive biomarker for early stage and stage specific breast cancer detection. To confirm that the expression of vitronectin is amplified in breast cancer, a total of 240 serum samples (n = 240), 200 from breast cancer patients and 40 controls were analyzed using the Reverse Phase Protein Array (RPPA) technique. Of the 240 samples, 120 samples were of African American (AA) descent, while the other 120 were of White American (WA) descent. Data indicated that there were some possible racial disparities in vitronectin levels and, differences also seen in the recurrent patient samples. Next, we tried to uncover the underlying mechanism which plays a critical role in vitronectin expression. The cellular data from four different breast cancer cell lines- MCF7, MDA-MB-231, MDA-MB-468, and HCC1599 indicated that the PI3K/AKT axis is modulating the expression of vitronectin. We believe that vitronectin concentration levels are involved and connected to the metastasis of breast cancer in certain patients, specifically based on recurrence or ethnicity, which is detrimental for poor prognosis. Therefore, in this current study we showed that the serum vitronectin levels could be an early marker for the breast cancer survival and we also determine the cellular signaling factors which modulate the expression and concentration of vitronectin.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Disease-Free Survival; Electrophoresis, Capillary; Ethnicity; Extracellular Matrix; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Neoplasm Recurrence, Local; Phosphatidylinositol 3-Kinases; ROC Curve; Vitronectin
PubMed: 33211735
DOI: 10.1371/journal.pone.0242141 -
Rheumatology International May 2015Osteoarthritis (OA) is a degenerative disease, which is characterized by articular cartilage destruction, and mainly affects the older people. The extracellular matrix... (Review)
Review
Osteoarthritis (OA) is a degenerative disease, which is characterized by articular cartilage destruction, and mainly affects the older people. The extracellular matrix (ECM) provides a vital cellular environment, and interactions between the cell and ECM are important in regulating many biological processes, including cell growth, differentiation, and survival. However, the pathogenesis of this disease is not fully elucidated, and it cannot be cured totally. Integrins are one of the major receptors in chondrocytes. A number of studies confirmed that the chondrocytes express several integrins including α5β1, αVβ3, αVβ5, α6β1, α1β1, α2β1, α10β1, and α3β1, and some integrins ligands might act as the OA progression biomarkers. This review focuses on the functional role of integrins and their extracellular ligands in OA progression, especially OA cartilage. Clear understanding of the role of integrins and their ligands in OA cartilage may have impact on future development of successful therapeutic approaches to OA.
Topics: Biomarkers; Cartilage, Articular; Chondrocytes; Extracellular Matrix; Fibronectins; Humans; Integrins; Osteoarthritis; Osteopontin; Tenascin; Vitronectin
PubMed: 25261047
DOI: 10.1007/s00296-014-3137-5 -
Materials Today. Bio Dec 2022Mesenchymal stem cell (MSC)-based tissue engineering strategies are of interest in the field of bone tissue regenerative medicine. MSCs are commonly investigated in...
Mesenchymal stem cell (MSC)-based tissue engineering strategies are of interest in the field of bone tissue regenerative medicine. MSCs are commonly investigated in combination with growth factors (GFs) and biomaterials to provide a regenerative environment for the cells. However, optimizing how biomaterials interact with MSCs and efficiently deliver GFs, remains a challenge. Here, via plasma polymerization, tissue culture plates are coated with a layer of poly (ethyl acrylate) (PEA), which is able to spontaneously permit fibronectin (FN) to form fibrillar nanonetworks. However, vitronectin (VN), another important extracellular matrix (ECM) protein forms multimeric globules on the polymer, thus not displaying functional groups to cells. Interestingly, when FN and VN are co-absorbed onto PEA surfaces, VN can be entrapped within the FN fibrillar nanonetwork in the monomeric form providing a heterogeneous, open ECM network. The combination of FN and VN promote MSC adhesion and leads to enhanced GF binding; here we demonstrate this with bone morphogenetic protein-2 (BMP2). Moreover, MSC differentiation into osteoblasts is enhanced, with elevated expression of osteopontin (OPN) and osteocalcin (OCN) quantified by immunostaining, and increased mineralization observed by von Kossa staining. Osteogenic intracellular signalling is also induced, with increased activity in the SMAD pathway. The study emphasizes the need of recapitulating the complexity of native ECM to achieve optimal cell-material interactions.
PubMed: 35937570
DOI: 10.1016/j.mtbio.2022.100367 -
Methods in Molecular Biology (Clifton,... 2021Myofibroblasts are critical to processes involved in normal wound healing and during pathological fibrosis. They transdifferentiate from fibroblasts, and in doing so...
Myofibroblasts are critical to processes involved in normal wound healing and during pathological fibrosis. They transdifferentiate from fibroblasts, and in doing so become contractile and capable of secreting large amounts of extracellular matrix proteins. Transforming growth factor-beta (TGFβ) is a key cytokine involved in wound healing and fibrogenesis. TGFβ signaling has long been the subject of experimental therapeutic approaches to inhibit fibrosis in a variety of organ systems. Inhibition of TGFβ can reduce myofibroblast transdifferentiation, contractility, and matrix production. Importantly, TGFβ is released from cells and sequestered in the extracellular matrix in a latent form that requires activation for biological function. There have been multiple mechanisms of TGFβ activation described in a variety of cell types and in cell free systems; however, myofibroblasts have previously been shown to activate TGFβ via cell surface integrins, particularly αvβ5 integrins. This chapter will provide detailed protocols for accurately measuring activation of TGFβ by myofibroblasts in vitro. Levels of active TGFβ usually represent a small proportion of the total amount of latent TGFβ present in the matrix. Methods to measure active TGFβ therefore need to be sensitive and specific to detect the active cytokine only.
Topics: Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Extracellular Matrix Proteins; Humans; Myofibroblasts; Receptors, Vitronectin; Signal Transduction; Transforming Growth Factor beta
PubMed: 34028736
DOI: 10.1007/978-1-0716-1382-5_6 -
Virus Research Jan 2024Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins...
Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins facilitate the ACE2-mediated cellular entry of SARS-CoV-2. We first tested the susceptibility of a panel of human cell lines to SARS-CoV-2 infection using the spike protein pseudotyped virus assay and examined the expression levels of integrins in these cell lines by qPCR, western blot and flow cytometry. We found that integrin αvβ1 was highly enriched in the SARS-CoV-2 susceptible cell lines. Additional studies demonstrated that RGD (403-405)→AAA mutant was defective in binding to integrin αvβ1 compared to its wild type counterpart, and anti-αvβ1 integrin antibodies significantly inhibited the entry of SARS-CoV-2 into the cells. Further studies using mouse NIH3T3 cells expressing human ACE2, integrin αv, integrin β1, and/or integrin αvβ1 suggest that integrin αvβ1 was unable to function as an independent receptor but could significantly facilitate the cellular entry of SASR-CoV-2. Finally, we observed that the Omicron exhibited a significant increase in the ACE2-mediated viral entry. Our findings may enhance our understanding of the pathogenesis of SARS-CoV-2 infection and offer potential therapeutic target for COVID-19.
Topics: Animals; Humans; Mice; Angiotensin-Converting Enzyme 2; COVID-19; NIH 3T3 Cells; Receptors, Vitronectin; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization
PubMed: 37884208
DOI: 10.1016/j.virusres.2023.199251 -
Immunological Reviews Jan 2016Phosphatidylserine recognition receptors are a highly diverse set of receptors grouped by their ability to recognize the 'eat-me' signal phosphatidylserine on apoptotic... (Review)
Review
Phosphatidylserine recognition receptors are a highly diverse set of receptors grouped by their ability to recognize the 'eat-me' signal phosphatidylserine on apoptotic cells. Most of the phosphatidylserine recognition receptors dampen inflammation by inducing the production of anti-inflammatory mediators during the phagocytosis of apoptotic corpses. However, many phosphatidylserine receptors are also capable of recognizing other ligands, with some receptors being categorized as scavenger receptors. It is now appreciated that these receptors can elicit different downstream events for particular ligands. Therefore, how phosphatidylserine recognition receptors mediate specific signals during recognition of apoptotic cells versus other ligands, and how this might help regulate the inflammatory state of a tissue is an important question that is not fully understood. Here, we revisit the work on signaling downstream of the phosphatidylserine recognition receptor BAI1, and evaluate how these and other signaling modules mediate signaling downstream from other receptors, including Stabilin-2, MerTK, and αvβ5. We also propose the concept that phosphatidylserine recognition receptors could be viewed as a subset of scavenger receptors that are capable of eliciting anti-inflammatory responses to apoptotic cells.
Topics: Angiogenic Proteins; Animals; Apoptosis; Cell Adhesion Molecules, Neuronal; Humans; Phagocytosis; Phosphatidylserines; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Receptors, G-Protein-Coupled; Receptors, Pattern Recognition; Receptors, Scavenger; Receptors, Vitronectin; Signal Transduction; c-Mer Tyrosine Kinase
PubMed: 26683144
DOI: 10.1111/imr.12376 -
Molecular Biology Reports Dec 2021In-stent restenosis usually occurs by platelet activation, neointima formation, VSMC migration, and proliferation in the position of the vessel stent. The monocytes have...
BACKGROUND
In-stent restenosis usually occurs by platelet activation, neointima formation, VSMC migration, and proliferation in the position of the vessel stent. The monocytes have a magnificent role in neointimal hyperplasia since these cells recruit to the site of vessel injury through chemokines and other secretion proteins. This study is focused on the investigation of vitronectin, miR-193, miR-34, and miR-520 expression levels in PBMCs isolated from stenosed patients.
METHODS
A total of sixty subjects undergoing coronary artery angiography containing patients with stent no restenosis (n = 20), in-stent restenosis (n = 20), and healthy participants (n = 20) participated in the study. The vitronectin, miR-193, miR-34, and miR-520 expression levels were measured by the RT-qPCR technique. Data were analyzed by SPSS software.
RESULTS
The vitronectin, miR-34, and miR-520 expression levels changed significantly in patients with vessel in-stent restenosis (p = 0.02, p = 0.02, and p = 0.01, respectively). Furthermore, there were inverse correlations between the expression levels of vitronectin gene and miR-34 (r = - 0.44, p = 0.04) as well as miR-520 (r = - 0.5, p=0.01).
CONCLUSIONS
The molecular events in the vessel stenosis may be affected by targeting vitronectin with miR-520 and miR-34.
Topics: Aged; Cell Movement; Constriction, Pathologic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Female; Gene Expression; Humans; Hyperplasia; Iran; Male; MicroRNAs; Middle Aged; Muscle, Smooth, Vascular; Neointima; Signal Transduction; Stents; Transcriptome; Vitronectin
PubMed: 34652615
DOI: 10.1007/s11033-021-06821-z -
Advances in Clinical and Experimental... Nov 2017Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a...
BACKGROUND
Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a multifunctional glycoprotein.
OBJECTIVES
The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc).
MATERIAL AND METHODS
Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-β levels were analyzed.
RESULTS
Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both).
CONCLUSIONS
These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.
Topics: Adult; Aged; Female; Humans; Interleukin-6; Male; Middle Aged; Osteopontin; Scleroderma, Systemic; Transforming Growth Factor beta; Vitronectin
PubMed: 29264880
DOI: 10.17219/acem/68627 -
Cell and Tissue Research Mar 2018Neutrophils, constituting the first line of defense, perform vital functions during immune surveillance. A key feature that assists in their prompt response to an... (Review)
Review
Neutrophils, constituting the first line of defense, perform vital functions during immune surveillance. A key feature that assists in their prompt response to an inflammatory signal is rapid migration to the affected site. They are normally short-lived but can be activated to live longer under the influence of an inflammatory stimulus. They can, thereby, release their toxic granule contents that are differentially housed inside the cytoplasm. Although these events are well characterized in the peripheral circulation, we are still far from fully understanding their recruitment in lungs. Lungs are a reservoir of neutrophils under steady-state. In the event of an infection or injury, they promptly activate and recruit to the alveolar compartment as well as the airways. Lung intravital microscopy has revealed that neutrophils display novel features during steady- and activated-state highlighting key differences in the lung vasculature compared to peripheral sites. This review will discuss neutrophil biology in lung inflammation and will highlight the role of angiostatin, an anti-angiogenic molecule, as well as vitronectin, an acute phase secreted plasma protein, in lung neutrophil recruitment.
Topics: Animals; Cell Movement; Humans; Lung; Models, Biological; Neutrophil Activation; Neutrophils; Pneumonia
PubMed: 29250746
DOI: 10.1007/s00441-017-2748-z