scholarly journals HIFα independent mechanisms in renal carcinoma cells modulate divergent outcomes in fibronectin assembly mediated by hypoxia and CoCl2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Carina Magdaleno ◽  
Leah Dixon ◽  
Narendiran Rajasekaran ◽  
Archana Varadaraj
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Matrix Protein ◽  
Tumor Hypoxia ◽  
Cell Types ◽  
Low Oxygen ◽  
Core Matrix ◽  
New Findings ◽  
The Matrix

Abstract Fibronectin (FN) is a core matrix protein that assembles to form a dynamic cellular scaffold, frequently perturbed during oncogenic transformation. Tumor hypoxia, characterized by low oxygen concentrations in the microenvironment of most solid tumors has been shown to accelerate FN assembly in fibroblasts and cancer-associated fibroblasts, cell types that produce abundant amounts of FN protein. Nevertheless, FN matrix regulation in epithelial cancer cells during hypoxia remains less well defined. In this study we investigate the assembly of the FN matrix during hypoxia in renal cancer epithelial cells, the cells of origin of renal cell carcinoma (RCC). We show that hypoxia (1% O2) specifically increases matrix disassembly and increases migratory propensity in renal cancer cells. However, HIFα stabilization using hypoxia mimetics, does not recapitulate the effect of hypoxia on FN matrix reorganization or cell migration. Using a combination of knockdown and inhibitor-based approaches, our work characterizes the signaling events that mediate these two disparate changes on the matrix and explores its functional significance on chemotactic cell migration. Our study systematically reexamines the role of hypoxia mimetics as experimental substitutes for hypoxia and provides new findings on HIFα stabilization and the FN matrix in the context of renal cancer.

scholarly journals The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts

2005 ◽  
Vol 171 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Viktor Todorovicç ◽  
Chih-Chiun Chen ◽  
Nissim Hay ◽  
Lester F. Lau
Keyword(s):  
Cell Adhesion ◽  
Cell Survival ◽  
Matrix Protein ◽  
De Novo ◽  
Cell Types ◽  
Cellular Interaction ◽  
Cytochrome C Release ◽  
The Matrix ◽  
Promote Cell Survival ◽  
Integrin Α6β1

Integrin-mediated cell adhesion to extracellular matrix proteins is known to promote cell survival, whereas detachment from the matrix can cause rapid apoptotic death in some cell types. Contrary to this paradigm, we show that fibroblast adhesion to the angiogenic matrix protein CCN1 (CYR61) induces apoptosis, whereas endothelial cell adhesion to CCN1 promotes cell survival. CCN1 induces fibroblast apoptosis through its adhesion receptors, integrin α6β1 and the heparan sulfate proteoglycan (HSPG) syndecan-4, triggering the transcription-independent p53 activation of Bax to render cytochrome c release and activation of caspase-9 and -3. Neither caspase-8 activity nor de novo transcription or translation is required for this process. These results show that cellular interaction with a specific matrix protein can either induce or suppress apoptosis in a cell type–specific manner and that integrin α6β1-HSPGs can function as receptors to induce p53-dependent apoptosis.

scholarly journals αvβ3 integrin expression up-regulates cdc2, which modulates cell migration

2003 ◽  
Vol 161 (4) ◽  
pp. 817-826 ◽  
Author(s):  
Thomas Manes ◽  
Duo-Qi Zheng ◽  
Simona Tognin ◽  
Amy S. Woodard ◽  
Pier Carlo Marchisio ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Ectopic Expression ◽  
Cell Types ◽  
Dominant Negative ◽  
Αvβ3 Integrin ◽  
Activity Levels ◽  
Mrna Levels ◽  
Downstream Effector

The αvβ3 integrin has been shown to promote cell migration through activation of intracellular signaling pathways. We describe here a novel pathway that modulates cell migration and that is activated by αvβ3 and, as downstream effector, by cdc2 (cdk1). We report that αvβ3 expression in LNCaP (β3-LNCaP) prostate cancer cells causes increased cdc2 mRNA levels as evaluated by gene expression analysis, and increased cdc2 protein and kinase activity levels. We provide three lines of evidence that increased levels of cdc2 contribute to a motile phenotype on integrin ligands in different cell types. First, increased levels of cdc2 correlate with more motile phenotypes of cancer cells. Second, ectopic expression of cdc2 increases cell migration, whereas expression of dominant-negative cdc2 inhibits migration. Third, cdc2 inhibitors reduce cell migration without affecting cell adhesion. We also show that cdc2 increases cell migration via specific association with cyclin B2, and we unravel a novel pathway of cell motility that involves, downstream of cdc2, caldesmon. cdc2 and caldesmon are shown here to localize in membrane ruffles in motile cells. These results show that cdc2 is a downstream effector of the αvβ3 integrin, and that it promotes cell migration.

scholarly journals Ingression-type cell migration drives vegetal endoderm internalisation in the Xenopus gastrula

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jason WH Wen ◽  
Rudolf Winklbauer
Keyword(s):  
Cell Migration ◽  
Large Scale ◽  
Matrix Protein ◽  
Cell Mass ◽  
Cell Formation ◽  
Germ Layer ◽  
Differential Migration ◽  
Cell Level ◽  
The Matrix ◽  
Shape Changes

During amphibian gastrulation, presumptive endoderm is internalised as part of vegetal rotation, a large-scale movement that encompasses the whole vegetal half of the embryo. It has been considered a gastrulation process unique to amphibians, but we show that at the cell level, endoderm internalisation exhibits characteristics reminiscent of bottle cell formation and ingression, known mechanisms of germ layer internalisation. During ingression proper, cells leave a single-layered epithelium. In vegetal rotation, the process occurs in a multilayered cell mass; we refer to it as ingression-type cell migration. Endoderm cells move by amoeboid shape changes, but in contrast to other instances of amoeboid migration, trailing edge retraction involves ephrinB1-dependent macropinocytosis and trans-endocytosis. Moreover, although cells are separated by wide gaps, they are connected by filiform protrusions, and their migration depends on C-cadherin and the matrix protein fibronectin. Cells move in the same direction but at different velocities, to rearrange by differential migration.

scholarly journals Unique Cancer Motility Behaviors in Confined Spaces of Microgroove Topography with Acute Wall Angles

2019 ◽  
Author(s):  
T. Yaginuma ◽  
K. Kushiro ◽  
M. Takai
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Acute Angle ◽  
The Body ◽  
Invasive Cancer ◽  
New Findings ◽  
Underlying Mechanisms ◽  
Different Response ◽  
Cancerous Cells

AbstractIn recent years, many types of micro-engineered platform have been fabricated to investigate the influences of surrounding microenvironments on cell migration. Previous researches demonstrate that microgroove-based topographies can influence cell motilities of normal and cancerous cells differently. In this paper, the microgroove wall angle is altered from obtuse to acute angles and the resulting differences in the responses of normal and cancer cells are investigated to explore the geometrical characteristics that can efficiently distinguish normal and cancer cells. Interestingly, trends in cell motilities of normal and cancer cells as the wall angles are varied between 60-120° were different, and in particular, invasive cancer cells exhibit a unique, oscillatory migratory behavior. Results from the immunostaining of cell mechanotransduction components suggest that this difference stems from directional extension and adhesion behaviors of each cell type. In addition, the specific behaviors of invasive cancer cells are found to be dependent on the myosin II activity, and modulating the activity can revert cancerous behaviors to normal ones. These novel findings on the interactions of acute angle walls and cancer cell migration provide a new perspective on cancer metastasis and additional strategies via microstructure geometries for the manipulations of cell behaviors in microscale biodevices.Statement of SignificanceCancer metastasis is the leading cause of cancer patient deaths, and yet how the microstructures within the body affect this cell migration phenomenon is not well understood. In this paper, microdevices containing microgroove structures of varying geometries, in particular obtuse and acute angles, were utilized to monitor cell motilities of various cancer cells to understand the influences of the geometrical features of microstructures on cancer metastasis. Surprisingly, it was found that the acute angle geometries lowered the persistence of migration for cancer cells, which was a totally different response from non-cancerous cells. These new findings would enable the next-generation biodevices to analyze, separate and capture cancer cells, as well as shed light onto the underlying mechanisms of cancer metastasis.

scholarly journals Bioengineering a novel 3D in-vitro model to recreate physiological oxygen levels and tumor-immune interactions

2019 ◽  
Author(s):  
Somshuvra Bhattacharya ◽  
Kristin Calar ◽  
Claire Evans ◽  
Mark Petrasko ◽  
Pilar de la Puente
Keyword(s):  
Immune Evasion ◽  
Matrix Protein ◽  
Tumor Hypoxia ◽  
Three Dimensional ◽  
Extracellular Vesicle ◽  
Extracellular Matrix Protein ◽  
Low Oxygen ◽  
Oxygen Levels ◽  
Induced Changes

ABSTRACTOxygen deprivation within tumors is one of the most prevalent causes of resilient cancer cell survival and increased immune evasion in breast cancer (BCa). Current in vitro models do not adequately mimic physiological oxygen levels relevant to breast tissue and its tumor-immune interactions. Here, we propose an approach to engineer a three-dimensional (3D) model (named 3D engineered oxygen, 3D-O) that supports growth of BCa cells and generates physio- and pathophysiological oxygen levels. Low oxygen-induced changes within the 3D-O model supported known tumor hypoxia characteristics such as reduced BCa cell proliferation, increased extracellular matrix protein expression, increased extracellular vesicle secretion and enhanced immune surface marker expression on BCa cells. We further demonstrated that low oxygen-induced changes mimicked tumor-immune interactions leading to immune evasion mechanisms. CD8+ T cell infiltration was significantly impaired under pathophysiological oxygen levels and we were able to establish that hypoxia inhibition re-sensitize BCa cells to cytotoxic CD8+ T cells. Therefore, our novel 3D-O model could serve as a promising platform for the evaluation of immunological events and as a drug-screening platform tool to overcome hypoxia-driven immune evasion.

scholarly journals Mesenchymal stem cells carry and transport clusters of cancer cells

2021 ◽  
Author(s):  
Jana Zarubova ◽  
Mohammad Mahdi Hasani-Sadrabadi ◽  
Sam CP Norris ◽  
Andrea M Kasko ◽  
Song Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cell Types ◽  
Cell Clusters ◽  
Different Cell Types

AbstractCell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of collective cell migration phenomenon and the involvement of different cell types during this process is needed. Here, we utilize a micropatterned surface composed of a thousand of low-adhesive microwells to screen motility of spheroids containing different cell types by analyzing their ability to move from the bottom to the top of the microwells. Mesenchymal stem cells (MSCs) spheroid migration was efficient in contrast to cancer cell only spheroids. In spheroids with both cell types mixed together, MSCs were able to carry the low-motile cancer cells during migration. As the percentage of MSCs increased in the spheroids, more migrating spheroids were detected. Extracellular vesicles secreted by MSCs also contributed to the pro-migratory effect exerted by MSCs. However, the transport of cancer cells was more efficient when MSCs were physically present in the cluster. Similar results were obtained when cell clusters were encapsulated within a micropatterned hydrogel, where collective migration was guided by micropatterned matrix stiffness. These results suggest that stromal cells facilitate the migration of cancer cell clusters, which is contrary to the general belief that malignant cells metastasize independently.SignificanceDuring metastasis, tumor cells may migrate as a cluster, which exhibit higher metastatic capacity compared to single cells. However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. Here, we utilize two unique approaches to study collective tumor cell migration in vitro: first, in low-adhesive microwells and second, in micropatterned hydrogels to analyze migration in 3D microenvironment. Our results indicate that MSCs in tumor cell clusters could play an important role in the dissemination of cancer cells by actively transporting low-motile cancer cells. In addition, MSC-released paracrine factors also increase the motility of tumor cells. These findings reveal a new mechanism of cancer cell migration and may lead to new approaches to suppress metastases.

scholarly journals Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin

2020 ◽  
Vol 118 (2) ◽  
pp. e2021366118
Author(s):  
Francesca Caccuri ◽  
Pasqualina D’Ursi ◽  
Matteo Uggeri ◽  
Antonella Bugatti ◽  
Pietro Mazzuca ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Molecular Mimicry ◽  
Cell Types ◽  
Biological Data ◽  
Matrix Proteins ◽  
Target Cells ◽  
Human Erythropoietin ◽  
The Matrix ◽  
The Difference ◽  
Hiv 1

The HIV-1 matrix protein p17 (p17) is a pleiotropic molecule impacting on different cell types. Its interaction with many cellular proteins underlines the importance of the viral protein as a major determinant of human specific adaptation. We previously showed the proangiogenic capability of p17. Here, by integrating functional analysis and receptor binding, we identify a functional epitope that displays molecular mimicry with human erythropoietin (EPO) and promotes angiogenesis through common beta chain receptor (βCR) activation. The functional EPO-like epitope was found to be present in the matrix protein of HIV-1 ancestors SIV originated in chimpanzees (SIVcpz) and gorillas (SIVgor) but not in that of HIV-2 and its ancestor SIVsmm from sooty mangabeys. According to biological data, evolution of the EPO-like epitope showed a clear differentiation between HIV-1/SIVcpz-gor and HIV-2/SIVsmm branches, thus highlighting this epitope on p17 as a divergent signature discriminating HIV-1 and HIV-2 ancestors. P17 is known to enhance HIV-1 replication. Similarly to other βCR ligands, p17 is capable of attracting and activating HIV-1 target cells and promoting a proinflammatory microenvironment. Thus, it is tempting to speculate that acquisition of an epitope on the matrix proteins of HIV-1 ancestors capable of triggering βCR may have represented a critical step to enhance viral aggressiveness and early human-to-human SIVcpz/gor dissemination. The hypothesis that the p17/βCR interaction and βCR abnormal stimulation may also play a role in sustaining chronic activation and inflammation, thus marking the difference between HIV-1 and HIV-2 in term of pathogenicity, needs further investigation.

scholarly journals The matrix protein CCN1/CYR61 is required for αVβ5-mediated cancer cell migration

2012 ◽  
Vol 30 (8) ◽  
pp. 687-695 ◽  
Author(s):  
Jana Jandova ◽  
Tracey E. Beyer ◽  
Emmanuelle J. Meuillet ◽  
George S. Watts
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Matrix Protein ◽  
Cancer Cell Migration ◽  
The Matrix

scholarly journals MT1-MMP-dependent cell migration: proteolytic and non-proteolytic mechanisms

2019 ◽  
Vol 47 (3) ◽  
pp. 811-826 ◽  
Author(s):  
Valentina Gifford ◽  
Yoshifumi Itoh
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Matrix Metalloproteinase ◽  
Cell Motility ◽  
Cell Types ◽  
Migration And Invasion ◽  
Type I ◽  
The Matrix ◽  
Increase Cell Motility ◽  
Dependent Cell

Abstract Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane proteinase that belongs to the matrix metalloproteinase (MMP) family. It is a potent modifier of cellular microenvironment and promotes cell migration and invasion of a wide variety of cell types both in physiological and pathological conditions. It promotes cell migration by degrading extracellular matrix on the cell surface and creates a migration path, by modifying cell adhesion property by shedding cell adhesion molecules to increase cell motility, and by altering cellular metabolism. Thus, MT1-MMP is a multifunctional cell motility enhancer. In this review, we will discuss the current understanding of the proteolytic and non-proteolytic mechanism of MT1-MMP-dependent cell migration.

Observations with the electron microscope on enameloid formation in the common eel ( Anguilla anguilla ; Teleostei)

1976 ◽  
Vol 194 (1115) ◽  
pp. 253-269 ◽  
Keyword(s):  
Matrix Protein ◽  
Basal Layer ◽  
Tooth Germ ◽  
Anguilla Anguilla ◽  
Cell Types ◽  
Secretory Cells ◽  
Oral Epithelium ◽  
Collagen Fibres ◽  
The Matrix ◽  
Cell Layers

In the eel, the very young tooth germ consisted of an invagination into the oral epithelium, filled with a papilla of mesenchymal cells. The basal layer of the epithelium surrounding the papilla became the inner dental epithelium (i. d. e.). Initially both the i. d. e. and the papilla cells were undifferentiated. Subsequently, the i. d. e. cells and the superficial cells of the papilla differentiated, the latter becoming odontoblasts, and the matrix of cap enameloid was laid down between the two cell layers. Differentiation of the i. d. e. cells and odontoblasts proceeded in parallel, both cell types acquiring the features of secretory cells, namely enlarged nucleoli, abundant rough endoplasmic reticulum, an active Golgi apparatus and numerous vesicles. Confluence of vesicles with the distal cell membranes was observed. These findings indicate that both the i. d. e. and odontoblasts synthesize protein and secrete it into the matrix of cap enameloid, in confirmation of previous studies with autoradiography (Shellis & Miles 1974). The matrix of cap enameloid reached its mature size and shape without becoming mineralized. It contained collagen fibres, odontoblast processes and vesicles. Mineralization of cap enameloid appeared to proceed centrifugally. The crystals were large and ribbon-like, as in enamel, and their orientation conformed with the pattern of collagen fibres of the matrix. The matrix protein, including the fibres, was, however, removed during mineralization, apparently by way of the i. d. e., which showed special features at this stage associated with transport of both protein and mineral. The collar enameloid in this fish was only about 2 μm thick and consisted of two hypermineralized layers. The inner layer appeared to be homologous with the cap enameloid, being formed by the joint activity of odontoblasts and the i. d. e. of Hertwig’s sheath. The outer, more heavily mineralized layer appeared to be produced entirely by the i. d. e. and a similar layer was laid down on the outer surface of the cap enameloid. The teeth of the eel thus bear a layer of enameloid, covered in turn by a much thinner layer which may be homologous with enamel.

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