scholarly journals Compressive Remodeling Alters Fluid Transport Properties of Collagen Networks – Implications for Tumor Growth

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
J. Ferruzzi ◽  
M. Sun ◽  
A. Gkousioudi ◽  
A. Pilvar ◽  
D. Roblyer ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Fluid Transport ◽  
Type I Collagen ◽  
Fluid Pressure ◽  
Hydraulic Permeability ◽  
Type I ◽  
Ecm Remodeling ◽  
Epithelial Cancers ◽  
The Matrix ◽  
Fluid Pressurization

AbstractBiomechanical alterations to the tumor microenvironment include accumulation of solid stresses, extracellular matrix (ECM) stiffening and increased fluid pressure in both interstitial and peri-tumoral spaces. The relationship between interstitial fluid pressurization and ECM remodeling in vascularized tumors is well characterized, while earlier biomechanical changes occurring during avascular tumor growth within the peri-tumoral ECM remain poorly understood. Type I collagen, the primary fibrous ECM constituent, bears load in tension while it buckles under compression. We hypothesized that tumor-generated compressive forces cause collagen remodeling via densification which in turn creates a barrier to convective fluid transport and may play a role in tumor progression and malignancy. To better understand this process, we characterized the structure-function relationship of collagen networks under compression both experimentally and computationally. Here we show that growth of epithelial cancers induces compressive remodeling of the ECM, documented in the literature as a TACS-2 phenotype, which represents a localized densification and tangential alignment of peri-tumoral collagen. Such compressive remodeling is caused by the unique features of collagen network mechanics, such as fiber buckling and cross-link rupture, and reduces the overall hydraulic permeability of the matrix.

Cytoskeleton and thyroglobulin expression change during transformation of thyroid epithelium to mesenchyme-like cells

Development ◽  
1988 ◽  
Vol 102 (3) ◽  
pp. 605-622 ◽  
Author(s):  
G. Greenburg ◽  
E.D. Hay
Keyword(s):  
Type I Collagen ◽  
Collagen Gel ◽  
Type I ◽  
Basal Cells ◽  
Collagen Gels ◽  
Expression Change ◽  
Cell Functions ◽  
The Matrix ◽  
3D Matrix ◽  
Mesenchymal Transformation

In considering the mechanism of transformation of epithelium to mesenchyme in the embryo, it is generally assumed that the ability to give rise to fibroblast-like cells is lost as epithelia mature. We reported previously that a definitive embryonic epithelium, that of the anterior lens, gives rise to freely migrating mesenchyme-like cells when suspended in type I collagen matrices. Here, we show that a highly differentiated epithelium that expresses cytokeratin changes to a vimentin cytoskeleton and loses thyroglobulin during epithelial-mesenchymal transformation induced by suspension in collagen gel. Using dispase and collagenase, we isolated adult thyroid follicles devoid of basal lamina and mesenchyme, and we suspended the follicles in 3D collagen gels. Cells bordering the follicle lumen retain epithelial polarity and thyroid phenotype, but basal cell surface organization is soon modified as a result of tissue multilayering and elongation of basal cells into the collagenous matrix. Cytodifferentiation, determined by thyroglobulin immunoreactivity, is lost as the basal epithelial cells move into the matrix after 3–4 days in collagen. By TEM, it can be seen that the elongating cells acquire pseudopodia, filopodia and mesenchyme-like nuclei and RER. Immunofluorescence examination of intermediate filaments showed that freshly isolated follicles and follicles cultured on planar substrata react only with anticytokeratin. However, all of the mesenchyme-like cells express vimentin and they gradually lose cytokeratin. These results suggest that vimentin may be necessary for cell functions associated with migration within a 3D matrix. The mesenchymal cells do not revert to epithelium when grown on planar substrata and the transformation of epithelium to mesenchyme-like cells does not occur within basement membrane gels. The results are relevant to our understanding of the initiation of epithelial-mesenchymal transformation in the embryo and the genetic mechanisms controlling cell shape, polarity and cytoskeletal phenotype.

Effect of subcellular matrix on glycosaminoglycan synthesis by human lung fibroblasts

1987 ◽  
Vol 63 (6) ◽  
pp. 2181-2188 ◽  
Author(s):  
D. J. Cui ◽  
B. A. Dubaybo ◽  
R. A. Durr ◽  
L. A. Thet
Keyword(s):  
Type I Collagen ◽  
Human Lung ◽  
Basement Membranes ◽  
Lung Fibroblasts ◽  
Type I ◽  
Glycosaminoglycan Synthesis ◽  
Human Lung Fibroblasts ◽  
Cell Matrix ◽  
Matrix Layer ◽  
The Matrix

The influences modulating glycosaminoglycan production by lung cells are not well understood. We examined the effect of three different subcellular matrices, plastic, type I collagen, and reconstituted basement membrane-like material (RBM), on the synthesis of sulfated glycosaminoglycans by cultured IMR-90 human lung fibroblasts. Accumulation of 35SO4-labeled glycosaminoglycans into the cell-matrix layer or medium was measured. Cells on collagen synthesized significantly less total glycosaminoglycans than cells on plastic but had a higher fraction of labeled glycosaminoglycans present in the cell-matrix layer (35 vs. 18%) with the increases being highest for dermatan and chondroitin sulfates. Cells grown on the RBM synthesized significantly more glycosaminoglycans than cells on plastic or collagen and also had 260% more labeled glycosaminoglycans present in the cell-matrix layer than cells on plastic. We conclude that the matrix to which lung fibroblasts are exposed can influence the amount and type of glycosaminoglycans synthesized and the degree of incorporation into the matrix. This may be relevant to fibrotic lungs with increased type I collagen or to severely injured lungs in which intra-alveolar fibroblasts are in contact with denuded basement membranes.

scholarly journals Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing

2019 ◽  
Vol 30 (17) ◽  
pp. 2218-2226 ◽  
Author(s):  
Jared T. Saunders ◽  
Jean E. Schwarzbauer
Keyword(s):  
Type I Collagen ◽  
Microscopic Analysis ◽  
Type I ◽  
Dependent Manner ◽  
Heparin Binding ◽  
Binding Studies ◽  
Matrix Assembly ◽  
Morphogenetic Protein ◽  
The Matrix ◽  
Heparin Binding Domain

The extracellular matrix (ECM) proteins fibronectin (FN) and type I collagen (collagen I) are codistributed in many tissues, and collagens have been shown to depend on an FN matrix for fibrillogenesis. Microscopic analysis of a fibroblast ECM showed colocalization of procollagen I with FN fibrils, and proteolytic cleavage of procollagen to initiate fibril formation was significantly reduced with inhibition of FN matrix assembly. We examined the role of FN matrix in procollagen processing by the C-propeptide proteinase bone morphogenetic protein 1 (BMP-1). We found that BMP-1 binds to a cell-assembled ECM in a dose-dependent manner and that, like procollagen, BMP-1 colocalizes with FN fibrils in the matrix microenvironment. Binding studies with FN fragments identified a binding site in FN’s primary heparin-binding domain. In solution, BMP-1–FN interactions and BMP-1 cleavage of procollagen I were both enhanced by the presence of heparin, suggesting a role for heparin in complex formation during proteolysis. Indeed, addition of heparin enhanced the rate of procollagen cleavage by matrix-bound BMP-1. Our results show that matrix localization of this proteinase facilitates the initiation of collagen assembly and suggest a model in which FN matrix and associated heparan sulfate act as a scaffold to organize enzyme and substrate for procollagen processing.

DDR2 induces linear invadosome to promote angiogenesis in a fibrillar type I collagen context

2020 ◽  
Author(s):  
Aya Abou Hammoud ◽  
Sébastien Marais ◽  
Nathalie Allain ◽  
Zakaria Ezzoukhry ◽  
Violaine Moreau ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Ex Vivo ◽  
Type I ◽  
Matrix Degradation ◽  
The Matrix ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor

AbstractTo generate new vessels, endothelial cells (ECs) form invadosomes, which are actin-based microdomains with a proteolytic activity that degrade the basement membrane. We previously demonstrated that ECs form linear invadosomes in fibrillar type I collagen context. In this study, we aim to investigate the molecular mechanisms by which ECs guides angiogenesis in a fibrillar type I collagen context. We found that Discoidin Domain Receptor 2 (DDR2) is the collagen receptor tyrosine kinase required to form linear invadosomes in ECs. We further demonstrated that it acts in synergy with VEGF to promote extracellular matrix degradation. We highlighted the involvement of an interaction between DDR2 and the matrix metalloproteinase MMP14 in this process. Finally, using in vitro and ex-vivo angiogenesis assays, we demonstrated a pro-angiogenic function of DDR2 in a collagen-rich microenvironment. This study allows us to propose DDR2-dependent linear invadosomes as targets to modulate angiogenesis.

scholarly journals Adhesion of platelets to laminin in the absence of activation.

1984 ◽  
Vol 99 (6) ◽  
pp. 2140-2145 ◽  
Author(s):  
C R Ill ◽  
E Engvall ◽  
E Ruoslahti
Keyword(s):  
Type I Collagen ◽  
Cell Attachment ◽  
Human Platelets ◽  
Type I ◽  
Initial Event ◽  
Serotonin Secretion ◽  
Platelet Binding ◽  
The Matrix ◽  
Subendothelial Matrix ◽  
Adhesion Of Platelets

The binding of platelets to components in the subendothelial matrix is an initial event in hemostasis and thrombosis. The glycoprotein components of the matrix are considered important in this interaction. Of these, collagen binds and activates platelets and induces their aggregation. In this study we demonstrate that substrate-bound laminin causes time- and concentration-dependent adherence of human platelets to the substrate. The binding of platelets to laminin was found to be similar in some respects, but different in others, to their binding to surfaces coated with fibronectin or collagen. The binding of platelets to laminin or fibronectin was not associated with their activation under conditions in which type I collagen activates the platelets as measured by [14C]serotonin secretion. Platelets bound to laminin and fibronectin differed in their appearance; they remained rounded on laminin whereas they flattened completely on fibronectin. Binding of platelets to fibronectin, but not laminin, is inhibited by a recently described peptide (Pierschbacher, M., and E. Ruoslahti, 1984, Nature (Lond.), 309:30-33) containing the cell-attachment tetrapeptide sequence of fibronectin, which suggests that separate receptors exist for laminin and fibronectin. These studies establish laminin as a platelet-binding protein and suggest that laminin can contribute to the adhesiveness of exposed tissue matrices to platelets. Since laminin and fibronectin do not activate platelets, whereas collagen does, and laminin differs from fibronectin in that it does not induce spreading of the attached platelets, all three proteins appear to confer different signals to the platelets. Some of these may be related to platelet functions other than those necessary for the formation of a hemostatic plug.

scholarly journals In situ localization and chromosomal mapping of the AG1 (Dmp1) gene.

1994 ◽  
Vol 42 (12) ◽  
pp. 1527-1531 ◽  
Author(s):  
A George ◽  
J Gui ◽  
N A Jenkins ◽  
D J Gilbert ◽  
N G Copeland ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Type I Collagen ◽  
Chromosomal Mapping ◽  
Human Tooth ◽  
Type I ◽  
Dentin Matrix Protein ◽  
Biomineralization Process ◽  
Tooth Mineralization ◽  
The Matrix

Dentinogenesis is being used as a model for understanding the biomineralization process. The odontoblasts synthesize a structural matrix comprised of Type I collagen fibrils which define the basic architecture of the tissue. The odontoblasts also synthesize and deliver a number of dentin-specific acidic macromolecules into the extracellular compartment. These acidic macromolecules may be involved in regulating the ordered deposition of hydroxyapatite crystals within the matrix. AG1 is the first tooth-specific acidic macromolecule to have been cloned and sequenced. To identify which cells of the rat incisor pulp/odontoblast complex were responsible for synthesis of AG1, in situ hybridization was used. Digoxigenin labeled sense and anti-sense AG1 riboprobes were prepared. The AG1 mRNA was found to be expressed in the mature secretory odontoblasts. Neither pulp cells nor pre-odontoblasts showed any staining with the anti-sense probes. Chromosomal localization studies placed the AG1 gene on mouse chromosome 5q21, in tight linkage with Fgf5. AG1 has been renamed Dmp1 (dentin matrix protein 1) in accordance with present chromosomal nomenclature. Mouse 5q21 corresponds to the 4q21 locus in humans. This is the locus for the human tooth mineralization disorder dentinogenesis imperfecta Type II (DI-II). These data suggest that the Dmp1 gene is involved in mineralization and is a candidate gene for DI-II.

scholarly journals Control of Bone Matrix Properties by Osteocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Amy Creecy ◽  
John G. Damrath ◽  
Joseph M. Wallace
Keyword(s):  
Type I Collagen ◽  
Bone Matrix ◽  
Type I ◽  
Bone Homeostasis ◽  
Surrounding Matrix ◽  
Matrix Properties ◽  
The Matrix ◽  
Exciting Potential

Osteocytes make up 90–95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts. Osteocytes are well positioned to play a role in bone homeostasis by interacting directly with the matrix; however, the ability for these cells to modify bone matrix remains incompletely understood. With techniques for examining the nano- and microstructure of bone matrix components including hydroxyapatite and type I collagen becoming more widespread, there is great potential to uncover novel roles for the osteocyte in maintaining bone quality. In this review, we begin with an overview of osteocyte biology and the lacunar–canalicular system. Next, we describe recent findings from in vitro models of osteocytes, focusing on the transitions in cellular phenotype as they mature. Finally, we describe historical and current research on matrix alteration by osteocytes in vivo, focusing on the exciting potential for osteocytes to directly form, degrade, and modify the mineral and collagen in their surrounding matrix.

Collagen-based biocomposites inspired by bone hierarchical structures advanced bone regeneration: Ongoing research and perspectives

2021 ◽  
Author(s):  
Di Qin ◽  
Na Wang ◽  
Xin-Guo You ◽  
Andi Zhang ◽  
Xiguang Chen ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Bone Regeneration ◽  
Hierarchical Structure ◽  
Type I Collagen ◽  
Hierarchical Structures ◽  
Collagen Fibers ◽  
Type I ◽  
Ongoing Research ◽  
The Matrix

Bone is a hard-connective tissue composed of matrix, cells and bioactive factors with hierarchical structure, where the matrix is mainly composed of type I collagen and hydroxyapatite. Collagen fibers assembled...

scholarly journals Loss of ADAM9 Leads to Modifications of the Extracellular Matrix Modulating Tumor Growth

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1290
Author(s):  
Anna N. Abety ◽  
Elke Pach ◽  
Nives Giebeler ◽  
Julia E. Fromme ◽  
Lavakumar Reddy Aramadhaka ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tumor Growth ◽  
Collagen Type ◽  
Tumor Stroma ◽  
Collagen Type I ◽  
Matrix Proteins ◽  
Transcriptional Level ◽  
Type I ◽  
Altered Expression ◽  
The Matrix

ADAM9 is a metalloproteinase strongly expressed at the tumor-stroma border by both tumor and stromal cells. We previously showed that the host deletion of ADAM9 leads to enhanced growth of grafted B16F1 melanoma cells by a mechanism mediated by TIMP1 and the TNF-α/sTNFR1 pathway. This study aimed to dissect the structural modifications in the tumor microenvironment due to the stromal expression of ADAM9 during melanoma progression. We performed proteomic analysis of peritumoral areas of ADAM9 deleted mice and identified the altered expression of several matrix proteins. These include decorin, collagen type XIV, fibronectin, and collagen type I. Analysis of these matrices in the matrix producing cells of the dermis, fibroblasts, showed that ADAM9−/− and wild type fibroblasts synthesize and secreted almost comparable amounts of decorin. Conversely, collagen type I expression was moderately, but not significantly, decreased at the transcriptional level, and the protein increased in ADAM9−/− fibroblast mono- and co-cultures with melanoma media. We show here for the first time that ADAM9 can release a collagen fragment. Still, it is not able to degrade collagen type I. However, the deletion of ADAM9 in fibroblasts resulted in reduced MMP-13 and -14 expression that may account for the reduced processing of collagen type I. Altogether, the data show that the ablation of ADAM9 in the host leads to the altered expression of peritumoral extracellular matrix proteins that generate a more favorable environment for melanoma cell growth. These data underscore the suppressive role of stromal expression of ADAM9 in tumor growth and call for a better understanding of how protease activities function in a cellular context for improved targeting.

Sign in / Sign up

Export Citation Format

Share Document