Vitronectin acts as a key regulator of adhesion and migration in umbilical cord-derived MSCs under different stress conditions

2021 ◽  
Author(s):  
Malancha Ta ◽  
Ankita Sen
Keyword(s):  
Cellular Therapy ◽  
Cellular Adhesion ◽  
Stress Conditions ◽  
Cellular Migration ◽  
Serum Starvation ◽  
Erk Pathway ◽  
Stress Fibre ◽  
Spread Area ◽  
And Migration ◽  
Cell Spread

Mesenchymal stem cell (MSC)-based cellular therapy gets compromised as adverse microenvironmental conditions like nutrient deprivation, ischemia, hypoxia affect migration and engraftment, in addition to viability, of MSCs at the target site post transplantation. To improve the treatment efficacy, it is critical to identify factors involved in regulating migration and adhesion of MSCs under such microenvironmental stress conditions. In our study, we observed that Wharton's jelly-MSCs (WJ-MSCs) exhibited increase in cell spread area and adhesion with reduction in cellular migration under serum starvation. The changes in adhesion and migration characteristics were accompanied by extensive stress fibre formation and altered ECM gene expression with notable induction in vitronectin (VTN) expression and reduction in MMP-1 expression. Molecular and phenotypic correlative studies advocated the possible role of VTN and not MMP-1, in regulating adhesion and migration of WJ-MSCs. NF-kb was found to be the positive regulator of VTN expression while ERK pathway regulated it negatively. Further investigation with inhibition of these signalling pathways or VTN knockdown studies under serum starvation established the correlation between increase in VTN expression and increased cellular adhesion with corresponding reduction in migration. VTN knockdown under serum starvation also led to reduction in actin stress fibre along with reversal in expression of several ECM genes. Additionally, VTN induction being absent in hypoxia-treated WJ-MSCs, the hypoxic cells showed no significant change in the adhesion and migration properties. However, when VTN expression was induced under hypoxia by ERK pathway inhibition, similar increase in cell spread area and adhesion was observed. Our study thus highlights VTN as a factor which is induced under serum starvation stress and possibly affects the adhesion and migration properties of WJ-MSCs.

scholarly journals Effects of a New Bioceramic Material on Human Apical Papilla Cells

2018 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Diana Sequeira ◽  
Catarina Seabra ◽  
Paulo Palma ◽  
Ana Cardoso ◽  
João Peça ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mineral Trioxide Aggregate ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cellular Viability ◽  
Migration Rates ◽  
Apical Papilla ◽  
And Migration ◽  
Proliferation And Migration

Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.

scholarly journals Differential Modulation of Matrix Metalloproteinases-2 and -7 in LAM/TSC Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1760
Author(s):  
Silvia Ancona ◽  
Emanuela Orpianesi ◽  
Clara Bernardelli ◽  
Eloisa Chiaramonte ◽  
Raffaella Chiaramonte ◽  
...  
Keyword(s):  
Epigenetic Modification ◽  
Lung Parenchyma ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Differential Modulation ◽  
Cystic Lung ◽  
Epidermal Growth ◽  
And Migration ◽  
Egfr Antibody

Matrix metalloproteinase (MMP) dysregulation is implicated in several diseases, given their involvement in extracellular matrix degradation and cell motility. In lymphangioleiomyomatosis (LAM), a pulmonary rare disease, MMP-2 and MMP-9 have been detected at high levels in serum and urine. LAM cells, characterized by a mutation in the tuberous sclerosis complex (TSC)1 or TSC2, promote cystic lung destruction. The role of MMPs in invasive and destructive LAM cell capability has not yet been fully understood. We evaluated MMP-2 and MMP-7 expression, secretion, and activity in primary LAM/TSC cells that bear a TSC2 germline mutation and an epigenetic modification and depend on epidermal growth factor (EGF) for survival. 5-azacytidine restored tuberin expression with a reduction of MMP-2 and MMP-7 levels and inhibits motility, similarly to rapamycin and anti-EGFR antibody. Both drugs reduced MMP-2 and MMP-7 secretion and activity during wound healing and decreased their expression in lung nodules of a LAM mouse model. In LAM/TSC cells, MMP-2 and MMP-7 are dependent on tuberin expression, cellular adhesion, and migration. MMPs appears sensitive to rapamycin and anti-EGFR antibody only during cellular migration. Our data indicate a complex and differential modulation of MMP-2 and MMP-7 in LAM/TSC cells, likely critical for lung parenchyma remodeling during LAM progression.

scholarly journals Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3181
Author(s):  
Ko-Hsiu Lu ◽  
Jia-Sin Yang ◽  
Yi-Hsien Hsieh ◽  
Hsiao-Ju Chu ◽  
Chia-Hsuan Chou ◽  
...  
Keyword(s):  
Cellular Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Erk Pathway ◽  
Lipocalin 2 ◽  
Cellular Motility ◽  
Osteosarcoma Cells ◽  
Cell Metastasis ◽  
Mitogen Activated Protein ◽  
And Migration

Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK–ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK–ERK pathway.

scholarly journals Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1781
Author(s):  
Beatrix Péter ◽  
Imre Boldizsár ◽  
Gábor M. Kovács ◽  
Anna Erdei ◽  
Zsuzsa Bajtay ◽  
...  
Keyword(s):  
Natural Compounds ◽  
Cellular Adhesion ◽  
Bioactive Metabolites ◽  
Label Free ◽  
Antiproliferative Effects ◽  
Receptor Sites ◽  
Measuring Techniques ◽  
Surface Receptor ◽  
And Migration ◽  
Active Substances

Plants and fungi can be used for medical applications because of their accumulation of special bioactive metabolites. These substances might be beneficial to human health, exerting also anti-inflammatory and anticancer (antiproliferative) effects. We propose that they are mediated by influencing cellular adhesion and migration via various signaling pathways and by directly inactivating key cell adhesion surface receptor sites. The evidence for this proposition is reviewed (by summarizing the natural metabolites and their effects influencing cellular adhesion and migration), along with the classical measuring techniques used to gain such evidence. We systematize existing knowledge concerning the mechanisms of how natural metabolites affect adhesion and movement, and their role in gene expression as well. We conclude by highlighting the possibilities to screen natural compounds faster and more easily by applying new label-free methods, which also enable a far greater degree of quantification than the conventional methods used hitherto. We have systematically classified recent studies regarding the effects of natural compounds on cellular adhesion and movement, characterizing the active substances according to their organismal origin (plants, animals or fungi). Finally, we also summarize the results of recent studies and experiments on SARS-CoV-2 treatments by natural extracts affecting mainly the adhesion and entry of the virus.

Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer

2018 ◽  
Vol 234 (1) ◽  
pp. 769-776 ◽  
Author(s):  
Ardavan Ghazanchaei ◽  
Behzad Mansoori ◽  
Ali Mohammadi ◽  
Alireza Biglari ◽  
Behzad Baradaran
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Erk Pathway ◽  
And Migration

scholarly journals Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf–MEK–ERK Pathway

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 326 ◽  
Author(s):  
Min-Hong Hsieh ◽  
Jia-Sin Yang ◽  
Renn-Chia Lin ◽  
Yi-Hsien Hsieh ◽  
Shun-Fa Yang ◽  
...  
Keyword(s):  
Presenilin 1 ◽  
Potential Candidate ◽  
Erk Pathway ◽  
Invasion And Migration ◽  
Cellular Invasion ◽  
Human Osteosarcoma ◽  
Extracellular Signal ◽  
Human Osteosarcoma Cells ◽  
U2os Cells ◽  
And Migration

Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway. Tomatidine, up to 100 μM, without cytotoxicity, inhibited the invasion and migration capabilities of human osteosarcoma U2OS and HOS cells and repressed presenilin 1 (PS-1) expression of U2OS cells. After the knockdown of PS-1, U2OS and HOS cells’ biological behaviors of cellular invasion and migratory potential were significantly reduced. While tomatidine significantly decreased the phosphorylation of c-Raf, mitogen/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated protein kinase (ERK)1/2 in U2OS cells, no obvious influences on p-Jun N-terminal kinase, p38, and Akt, including their phosphorylation, were observed. In ERK 1 silencing U2 OS cells, tomatidine further enhanced the decrease of their migratory potential and invasive activities. We conclude that both PS-1 derived from U2OS and HOS cells and the c-Raf–MEK–ERK pathway contribute to cellular invasion and migration and tomatidine could inhibit the phenomenons. These findings indicate that tomatidine might be a potential candidate for anti-metastasis treatment of human osteosarcoma.

scholarly journals Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

2010 ◽  
Vol 190 (4) ◽  
pp. 675-691 ◽  
Author(s):  
Mark T. Howes ◽  
Matthew Kirkham ◽  
James Riches ◽  
Katia Cortese ◽  
Piers J. Walser ◽  
...  
Keyword(s):  
High Capacity ◽  
Leading Edge ◽  
Cellular Adhesion ◽  
Endocytic Pathway ◽  
Membrane Turnover ◽  
Major Pathway ◽  
Endocytic Sorting ◽  
And Migration ◽  
Sorting Station ◽  
Migrating Cells

Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.

Biological Mechanisms for Cartilage Repair Using a BioCartilage Scaffold: Cellular Adhesion/Migration and Bioactive Proteins

Cartilage ◽  
2020 ◽  
pp. 194760351990080 ◽  
Author(s):  
Jacqueline Commins ◽  
Rebecca Irwin ◽  
Andrea Matuska ◽  
Margaret Goodale ◽  
Michelle Delco ◽  
...  
Keyword(s):  
Fibrin Glue ◽  
Cartilage Repair ◽  
Matrix Protein ◽  
Cell Attachment ◽  
Interleukin 1 ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cartilage Explants ◽  
Cartilage Defects ◽  
Bioactive Proteins

Objective. BioCartilage is a desiccated, particulated cartilage allograft used for repair of focal cartilage defects. It is mixed with a biologic such as bone marrow concentrate (BMC), pressed into a contained defect, and sealed with fibrin glue. The objective of this study was to assess if BioCartilage could serve as a bioactive scaffold by affecting cellular adhesion, cellular migration, or the release interleukin-1 receptor antagonist protein (IL-1RA), and to identify its full proteomic makeup. Design. Cartilage explants were used to model confined defects. BioCartilage was mixed with BMC, grafted into defects, and sealed with 1 of 5 fibrin glues. Constructs were cultured for 24 or 48 hours and then processed for live/dead microscopy. Chondrocyte and mesenchymal stem cell (MSC) adhesion on BioCartilage was assessed using scanning electron microscopy. Conditioned medium from cultures and the biologics used in the study were assayed for IL-1RA. The protein footprint of BioCartilage was determined using bottom-up proteomics. Results. BioCartilage supported chondrocyte and MSC attachment within 24 hours, and cell viability was retained in all constructs at 24 and 48 hours. Fibrin glue did not inhibit cell attachment. BMC had the highest concentration of IL-1RA. Proteomics yielded 254 proteins, including collagens, proteoglycans, and several bioactive proteins with known anabolic roles including cartilage oligomeric matrix protein. Conclusions. This study suggests that BioCartilage has the chemical composition and architecture to support cell adherence and migration and to provide bioactive proteins, which together should have biologics advantages in cartilage repair beyond its role as a scaffold.

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