scholarly journals Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

2020 ◽  
Vol 21 (5) ◽  
pp. 1749 ◽  
Author(s):  
Thomas J. Bauer ◽  
Erich Gombocz ◽  
Markus Wehland ◽  
Johann Bauer ◽  
Manfred Infanger ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Binding Activity ◽  
Omics Data ◽  
Adhesion Proteins ◽  
Adhesion Behavior

The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins’ glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.

scholarly journals Mechanisms of endothelial cell coverage by pericytes: computational modelling of cell wrapping and in vitro experiments

2020 ◽  
Vol 17 (162) ◽  
pp. 20190739
Author(s):  
Kei Sugihara ◽  
Saori Sasaki ◽  
Akiyoshi Uemura ◽  
Satoru Kidoaki ◽  
Takashi Miura
Keyword(s):  
Cell Adhesion ◽  
Three Dimensional ◽  
Computational Modelling ◽  
Cellular Level ◽  
Cellular Potts Model ◽  
Contributing Factors ◽  
Modelling Framework ◽  
Cell Cell

Pericytes (PCs) wrap around endothelial cells (ECs) and perform diverse functions in physiological and pathological processes. Although molecular interactions between ECs and PCs have been extensively studied, the morphological processes at the cellular level and their underlying mechanisms have remained elusive. In this study, using a simple cellular Potts model, we explored the mechanisms for EC wrapping by PCs. Based on the observed in vitro cell wrapping in three-dimensional PC–EC coculture, the model identified four putative contributing factors: preferential adhesion of PCs to the extracellular matrix (ECM), strong cell–cell adhesion, PC surface softness and larger PC size. While cell–cell adhesion can contribute to the prevention of cell segregation and the degree of cell wrapping, it cannot determine the orientation of cell wrapping alone. While atomic force microscopy revealed that PCs have a larger Young’s modulus than ECs, the experimental analyses supported preferential ECM adhesion and size asymmetry. We also formulated the corresponding energy minimization problem and numerically solved this problem for specific cases. These results give biological insights into the role of PC–ECM adhesion in PC coverage. The modelling framework presented here should also be applicable to other cell wrapping phenomena observed in vivo .

scholarly journals Direct interaction of metastasis-inducing S100P protein with tubulin causes enhanced cell migration without changes in cell adhesion

2020 ◽  
Vol 477 (6) ◽  
pp. 1159-1178
Author(s):  
Min Du ◽  
Guozheng Wang ◽  
Igor L. Barsukov ◽  
Stephane R. Gross ◽  
Richard Smith ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Hela Cells ◽  
Cancer Metastasis ◽  
Dissociation Constants ◽  
Breast Cancer Metastasis ◽  
Breast Cancers ◽  
Β Tubulin

Overexpression of S100P promotes breast cancer metastasis in animals and elevated levels in primary breast cancers are associated with poor patient outcomes. S100P can differentially interact with nonmuscle myosin (NM) isoforms (IIA > IIC > IIB) leading to the redistribution of actomyosin filaments to enhance cell migration. Using COS-7 cells which do not naturally express NMIIA, S100P is now shown to interact directly with α,β-tubulin in vitro and in vivo with an equilibrium Kd of 2–3 × 10−7 M. The overexpressed S100P is located mainly in nuclei and microtubule organising centres (MTOC) and it significantly reduces their number, slows down tubulin polymerisation and enhances cell migration in S100P-induced COS-7 or HeLa cells. It fails, however, to significantly reduce cell adhesion, in contrast with NMIIA-containing S100P-inducible HeLa cells. When taxol is used to stabilise MTs or colchicine to dissociate MTs, S100P's stimulation of migration is abolished. Affinity-chromatography of tryptic digests of α and β-tubulin on S100P-bound beads identifies multiple S100P-binding sites consistent with S100P binding to all four half molecules in gel-overlay assays. When screened by NMR and ITC for interacting with S100P, four chemically synthesised peptides show interactions with low micromolar dissociation constants. The two highest affinity peptides significantly inhibit binding of S100P to α,β-tubulin and, when tagged for cellular entry, also inhibit S100P-induced reduction in tubulin polymerisation and S100P-enhancement of COS-7 or HeLa cell migration. A third peptide incapable of interacting with S100P also fails in this respect. Thus S100P can interact directly with two different cytoskeletal filaments to independently enhance cell migration, the most important step in the metastatic cascade.

scholarly journals Aspirin suppresses components of lymphangiogenesis and lymphatic vessel remodeling by inhibiting the NF-κB/VCAM-1 pathway in human lymphatic endothelial cells

2018 ◽  
Vol 23 (3) ◽  
pp. 201-211 ◽  
Author(s):  
Orawin Prangsaengtong ◽  
Phatcharida Jantaree ◽  
Kriengsak Lirdprapamongkol ◽  
Lukana Ngiwsara ◽  
Jisnuson Svasti ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Lymphatic Vessels ◽  
Mrna Levels ◽  
Lymphatic Endothelial Cells ◽  
Tubule Formation ◽  
Toxic Dose

Lymphangiogenesis is the process of new vessel formation from pre-existing lymphatic vessels. The process mainly involves cell adhesion, migration, and tubule formation of lymphatic endothelial cells. Tumor-induced lymphangiogenesis is an important factor contributing to promotion of tumor growth and cancer metastasis via the lymphatic system. Finding the non-toxic agents that can prevent or inhibit lymphangiogenesis may lead to blocking of lymphatic metastasis. Recently, aspirin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to inhibit in vivo lymphangiogenesis in tumor and incision wound models, but the mechanisms of actions of aspirin on anti-lymphangiogenesis have been less explored. In this study, we aim to explore the mechanism underlying the anti-lymphangiogenic effects of aspirin in primary human dermal lymphatic microvascular endothelial (HMVEC-dLy) cells in vitro. Pretreatment of aspirin at non-toxic dose 0.3 mM significantly suppressed in vitro cord formation, adhesion, and the migration abilities of the HMVEC-dLy cells. Western blotting analysis indicated that aspirin decreased expression of vascular cell adhesion molecule-1 (VCAM-1), at both protein and mRNA levels, and these correlated with the reduction of NF-κB p65 phosphorylation. By using NF-κB inhibitor (BAY-11-7085) and VCAM-1 siRNA, we showed that VCAM-1 expression is downstream of NF-κB activation, and this NF-κB/VCAM-1 signaling pathway controls cord formation, adhesion, and the migration abilities of the HMVEC-dLy cells. In summary, we demonstrate the potential of aspirin as an anti-lymphangiogenic agent, and elucidate its mechanism of action.

scholarly journals Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Indira Sigdel ◽  
Niraj Gupta ◽  
Fairuz Faizee ◽  
Vishwa M. Khare ◽  
Amit K. Tiwari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Studies ◽  
Cancer Metastasis ◽  
Three Dimensional ◽  
Breast Cancer Metastasis ◽  
Therapeutic Interventions ◽  
Special Focus ◽  
Cellular Interactions

Of around half a million women dying of breast cancer each year, more than 90% die due to metastasis. Models necessary to understand the metastatic process, particularly breast cancer cell extravasation and colonization, are currently limited and urgently needed to develop therapeutic interventions necessary to prevent breast cancer metastasis. Microfluidic approaches aim to reconstitute functional units of organs that cannot be modeled easily in traditional cell culture or animal studies by reproducing vascular networks and parenchyma on a chip in a three-dimensional, physiologically relevantin vitrosystem. In recent years, microfluidics models utilizing innovative biomaterials and micro-engineering technologies have shown great potential in our effort of mechanistic understanding of the breast cancer metastasis cascade by providing 3D constructs that can mimicin vivocellular microenvironment and the ability to visualize and monitor cellular interactions in real-time. In this review, we will provide readers with a detailed discussion on the application of the most up-to-date, state-of-the-art microfluidics-based breast cancer models, with a special focus on their application in the engineering approaches to recapitulate the metastasis process, including invasion, intravasation, extravasation, breast cancer metastasis organotropism, and metastasis niche formation.

scholarly journals Transcriptional suppression of AMPKα1 promotes breast cancer metastasis upon oncogene activation

2020 ◽  
Vol 117 (14) ◽  
pp. 8013-8021 ◽  
Author(s):  
Yong Yi ◽  
Deshi Chen ◽  
Juan Ao ◽  
Wenhua Zhang ◽  
Jianqiao Yi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Kinase Activity ◽  
Critical Role ◽  
Breast Cancer Metastasis ◽  
Transcription Control ◽  
Cell Cell

AMP-activated protein kinase (AMPK) functions as an energy sensor and is pivotal in maintaining cellular metabolic homeostasis. Numerous studies have shown that down-regulation of AMPK kinase activity or protein stability not only lead to abnormality of metabolism but also contribute to tumor development. However, whether transcription regulation of AMPK plays a critical role in cancer metastasis remains unknown. In this study, we demonstrate that AMPKα1 expression is down-regulated in advanced human breast cancer and is associated with poor clinical outcomes. Transcription of AMPKα1 is inhibited on activation of PI3K and HER2 through ΔNp63α. Ablation of AMPKα1 expression or inhibition of AMPK kinase activity leads to disruption of E-cadherin-mediated cell–cell adhesion in vitro and increased tumor metastasis in vivo. Furthermore, restoration of AMPKα1 expression significantly rescues PI3K/HER2-induced disruption of cell–cell adhesion, cell invasion, and cancer metastasis. Together, these results demonstrate that the transcription control is another layer of AMPK regulation and suggest a critical role for AMPK in regulating cell–cell adhesion and cancer metastasis.

scholarly journals CircURI1 interacts with hnRNPM to inhibit metastasis by modulating alternative splicing in gastric cancer

2021 ◽  
Vol 118 (33) ◽  
pp. e2012881118
Author(s):  
Xiaolin Wang ◽  
Jingxin Li ◽  
Xing Bian ◽  
Cheng Wu ◽  
Jinghan Hua ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Alternative Splicing ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Nuclear Ribonucleoprotein

Circular RNAs (circRNAs) have emerged as key regulators of human cancers, yet their modes of action in gastric cancer (GC) remain largely unknown. Here, we identified circURI1 back-spliced from exons 3 and 4 of unconventional prefoldin RPB5 interactor 1 (URI1) from circRNA profiling of five-paired human gastric and the corresponding nontumor adjacent specimens (paraGC). CircURI1 exhibits the significantly higher expression in GC compared with paraGC and inhibitory effects on cell migration and invasion in vitro and GC metastasis in vivo. Mechanistically, circURI1 directly interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM) to modulate alternative splicing of genes, involved in the process of cell migration, thus suppressing GC metastasis. Collectively, our study expands the current knowledge regarding the molecular mechanism of circRNA-mediated cancer metastasis via modulating alternative splicing.

scholarly journals Avian Reovirus P17 Suppresses Angiogenesis by Promoting DPP4 Secretion

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 259
Author(s):  
Ekta Manocha ◽  
Antonella Bugatti ◽  
Mirella Belleri ◽  
Alberto Zani ◽  
Stefania Marsico ◽  
...  
Keyword(s):  
Viral Protein ◽  
Cancer Metastasis ◽  
Three Dimensional ◽  
Avian Reovirus ◽  
Structural Protein ◽  
Antitumor Activities ◽  
Dipeptidyl Peptidase 4 ◽  
New Therapeutic Approaches

Avian reovirus p17 (ARV p17) is a non-structural protein known to activate autophagy, interfere with gene transcription and induce a significant tumor cell growth inhibition in vitro and in vivo. In this study, we show that ARV p17 is capable of exerting potent antiangiogenic properties. The viral protein significantly inhibited the physiological angiogenesis of human endothelial cells (ECs) by affecting migration, capillary-like structure and new vessel formation. ARV p17 was not only able to suppress the EC physiological angiogenesis but also rendered ECs insensitive to two different potent proangiogenic inducers, such as VEGF-A and FGF-2 in the three-dimensional (3D) Matrigel and spheroid assay. ARV p17 was found to exert its antiangiogenic activity by upregulating transcription and release of the well-known tumor suppressor molecule dipeptidyl peptidase 4 (DPP4). The ability of ARV p17 to impact on angiogenesis is completely new and highlights the “two compartments” activity of the viral protein that is expected to hamper the tumor parenchymal/stromal crosstalk. The complex antitumor activities of ARV p17 open the way to a new promising field of research aimed to develop new therapeutic approaches for treating tumor and cancer metastasis.

scholarly journals An Insight into the Anti-Angiogenic and Anti-Metastatic Effects of Oridonin: Current Knowledge and Future Potential

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 775
Author(s):  
Nurul Akmaryanti Abdullah ◽  
Nur Fariesha Md Hashim ◽  
Aula Ammar ◽  
Noraina Muhamad Zakuan
Keyword(s):  
Cancer Therapy ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Angiogenic Growth Factors ◽  
Mesenchymal Transition ◽  
Anti Cancer

Cancer is one of the leading causes of death worldwide, with a mortality rate of more than 9 million deaths reported in 2018. Conventional anti-cancer therapy can greatly improve survival however treatment resistance is still a major problem especially in metastatic disease. Targeted anti-cancer therapy is increasingly used with conventional therapy to improve patients’ outcomes in advanced and metastatic tumors. However, due to the complexity of cancer biology and metastasis, it is urgent to develop new agents and evaluate the anti-cancer efficacy of available treatments. Many phytochemicals from medicinal plants have been reported to possess anti-cancer properties. One such compound is known as oridonin, a bioactive component of Rabdosia rubescens. Several studies have demonstrated that oridonin inhibits angiogenesis in various types of cancer, including breast, pancreatic, lung, colon and skin cancer. Oridonin’s anti-cancer effects are mediated through the modulation of several signaling pathways which include upregulation of oncogenes and pro-angiogenic growth factors. Furthermore, oridonin also inhibits cell migration, invasion and metastasis via suppressing epithelial-to-mesenchymal transition and blocking downstream signaling targets in the cancer metastasis process. This review summarizes the recent applications of oridonin as an anti-angiogenic and anti-metastatic drug both in vitro and in vivo, and its potential mechanisms of action.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

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