Faculty Opinions recommendation of Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and promotes proliferation of pancreatic carcinoma cells.

Chondrocytes in articular cartilage synthesize collagen type II and large sulfated proteoglycans, whereas the same cells cultured in monolayer (2D) dedifferentiate into fibroblastic cells and express collagen type I and small proteoglycans. On the other hand, a pellet culture system was developed as a method for preventing the phenotypic modulation of chondrocytes and promoting the redifferentiation of dedifferentiated ones. Because the pellet culture system forms only one cell aggregate each tube by a centrifugator, the pellet could not be applied to produce a tissue-engineered cartilage. Therefore, we tried to form chondrocyte aggregates by a rotational culture, expecting to form a large number of aggregates at once. In order to increase cell–cell interactions and decrease chondrocyte–material interaction, dishes with low retention of protein adsorption and cell adhesiveness were used. In addition, rotational shaking of the dish including cells was attempted to increase the cell–cell interaction. The shaking speed was set at 80 rpm, so the cells would be distributed in the center of the dish to augment the frequency of cell–cell contact. Under these conditions, bovine articular chondrocytes started aggregating in a few hours. At 24–36 h of rotational culture, aggregates with smooth surfaces were observed. Parameters such as increase of culture time and addition of TGF-β controlled diameters of the aggregates. There were many fusiform cells at the periphery of the aggregates, where the cells tended to form a multilayered zone in cross sections. In addition, lacune-like structure, which was almost the same as pellet culture, was observed. It was found that the internal structure of the aggregates was similar to that of pellets reported previously. Therefore, the aggregates formed by a rotational culture could become an essential component to make tissue-engineered artificial cartilage.

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Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer

Oncogene ◽

10.1038/sj.onc.1210012 ◽

2006 ◽

Vol 26 (16) ◽

pp. 2381-2385 ◽

Cited By ~ 76

Author(s):

Y Imamichi ◽

A König ◽

T Gress ◽

A Menke

Keyword(s):

Pancreatic Cancer ◽

Collagen Type ◽

Collagen Type I ◽

Type I ◽

Interacting Protein ◽

E Cadherin

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Oncostatin M-induced effects on EMT in human proximal tubular cells: differential role of ERK signaling

AJP Renal Physiology ◽

10.1152/ajprenal.00130.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. F1714-F1726 ◽

Cited By ~ 39

Author(s):

Verena Pollack ◽

Rita Sarközi ◽

Zoltan Banki ◽

Elisabeth Feifel ◽

Swantje Wehn ◽

...

Keyword(s):

Collagen Type ◽

Collagen Type I ◽

Oncostatin M ◽

Type I ◽

Proximal Tubular Cells ◽

Strong Concentration ◽

Tubular Cells ◽

Cell Scattering ◽

Proximal Tubular ◽

E Cadherin

Growing evidence suggests that a proportion of interstitial myofibroblasts detected during renal tubulointerstitial fibrosis originates from tubular epithelial cells by a process called epithelial-mesenchymal transition (EMT). The IL-6-type cytokine oncostatin M (OSM) has been recently implicated in the induction of EMT. We investigated OSM effects on the expression of both cell-cell contact proteins and mesenchymal markers and studied OSM-induced intracellular signaling mechanisms associated with these events in human proximal tubular cells. Human recombinant OSM attenuated the expression of N-cadherin, E-cadherin, and claudin-2 in human kidney-2 (HK-2) cells associated with the induction of HK-2 cell scattering in 3D collagen matrices. Conversely, expression of collagen type I, vimentin, and S100A4 was induced by OSM. OSM-stimulated cell scattering was inhibited by antibodies against gp130. Besides inducing phosphorylation of Stat1 and Stat3, OSM led to a strong concentration- and time-dependent phosphorylation of the mitogen-activated protein kinases ERK1, ERK2, and ERK5. MEK1/2 inhibitor U0126 (10 μM) blocked basal and OSM-induced ERK1/2 phosphorylation but not phosphorylation of either ERK5 or Stat1/3. Both synthetic MEK1/2 inhibitors U0126 and Cl-1040, when used at concentrations which inhibit ERK1/2 phosphorylation but not ERK5 phosphorylation, restored N-cadherin expression in the presence of OSM, inhibited basal claudin-2 expression, but did not affect either basal or OSM-inhibited E-cadherin expression or OSM-induced expression of collagen type I and vimentin. These results suggest that in human proximal tubular cells ERK1/2 signaling represents an important component of OSM's inhibitory effect on N-cadherin expression. Furthermore, functional ERK1/2 signaling is necessary for basal claudin-2 expression.

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Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1

Journal of Cell Science ◽

10.1242/jcs.114.1.111 ◽

2001 ◽

Vol 114 (1) ◽

pp. 111-118 ◽

Cited By ~ 5

Author(s):

V. Noe ◽

B. Fingleton ◽

K. Jacobs ◽

H.C. Crawford ◽

S. Vermeulen ◽

...

Keyword(s):

Cell Adhesion ◽

Cell Surface ◽

Collagen Type ◽

Cell Aggregation ◽

Collagen Type I ◽

Type I ◽

Tissue Inhibitor Of Metalloproteinases ◽

Dependent Cell ◽

Mcf 7 ◽

E Cadherin

The function of many transmembrane molecules can be altered by cleavage and subsequent release of their ectodomains. We have investigated ectodomain cleavage of the cell-cell adhesion and signal-transducing molecule E-cadherin. The E-cadherin ectodomain is constitutively shed from the surface of MCF-7 and MDCKts.srcC12 cells in culture. Release of the 80 kDa soluble E-cadherin fragment is stimulated by phorbol-12-myristate-13-acetate and is inhibited by overexpression of the tissue inhibitor of metalloproteinases-2. The metalloproteinases matrilysin and stromelysin-1 both cleave E-cadherin at the cell surface and release sE-CAD into the medium. The soluble E-cadherin fragment thus released inhibits E-cadherin functions in a paracrine way, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation. Our results, therefore, suggest a novel mechanism by which metalloproteinases can influence invasion.

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The TGF-β1 Signaling Pathway as an Attractive Target in the Fibrosis Pathogenesis of Sjögren’s Syndrome

Mediators of Inflammation ◽

10.1155/2018/1965935 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Margherita Sisto ◽

Loredana Lorusso ◽

Giuseppe Ingravallo ◽

Roberto Tamma ◽

Domenico Ribatti ◽

...

Keyword(s):

Signaling Pathway ◽

Collagen Type ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Collagen Type I ◽

Sjogren's Syndrome ◽

Type I ◽

Protein Levels ◽

Sjögren‘S Syndrome ◽

E Cadherin

Transforming growth factor β1 (TGF-β1) plays a crucial role in the induction of fibrosis, often associated with chronic phases of inflammatory diseases contributing to marked fibrotic changes that compromise normal organ function. The TGF-β1 signal exerts its biological effects via the TGF-β/SMAD/Snail signaling pathway, playing an important pathogenic role in several fibrotic diseases. It has as yet been poorly investigated in the chronic autoimmune disease Sjögren’s syndrome (SS). Here, we firstly tested, by immunohistochemistry, whether the TGF-β1/SMAD/Snail signaling pathway is triggered in human pSS salivary glands (SGs). Next, healthy salivary gland epithelial cell (SGEC) cultures derived from healthy donors were exposed to TGF-β1 treatment, and the relative gene and protein levels of SMAD2/3/4, Snail, E-cadherin, vimentin, and collagen type I were compared by semiquantitative RT-PCR, quantitative real-time PCR, and Western blot analysis. We observed, both at gene and protein levels, higher expression of SMAD2, 3, and 4 and Snail in the SGEC exposed by TGF-β1 compared to untreated healthy SGEC. Additionally, in TGF-β1-treated samples, we found a significant reduction in the epithelial phenotype marker E-cadherin and an increase in the mesenchymal phenotype markers vimentin and collagen type I compared to those in untreated SGEC, indicating that TGF-β1 induces the EMT via the TGF-β1/SMAD/Snail signaling pathway. Therefore, by using the specific TGF-β receptor 1 inhibitor SB-431542 in healthy SGEC treated with TGF-β1, we showed a significant reduction of the fibrosis markers vimentin and collagen type I while the epithelial marker E-cadherin returns to levels similar to untreated healthy SGEC. These data demonstrate that TGF-β1 is an important key factor in the transition phase from SG chronic inflammation to fibrotic disease. Characteristic changes in the morphology and function of TGF-β1-treated healthy SGEC further confirm that TGF-β1 plays a significant role in EMT-dependent fibrosis.

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Functional interaction between E-cadherin and alphav-containing integrins in carcinoma cells

Journal of Cell Science ◽

10.1242/jcs.113.3.425 ◽

2000 ◽

Vol 113 (3) ◽

pp. 425-437 ◽

Cited By ~ 2

Author(s):

M. von Schlippe ◽

J.F. Marshall ◽

P. Perry ◽

M. Stone ◽

A.J. Zhu ◽

...

Keyword(s):

Morphological Changes ◽

Surface Expression ◽

Collagen Type I ◽

Carcinoma Cells ◽

Dominant Negative ◽

Type I ◽

Beta Catenin ◽

Receptor Aggregation ◽

E Cadherin

We have demonstrated the possibility of cross-talk between E-cadherin and alphav integrins in breast carcinoma cells. Using the function-blocking anti-alphav monoclonal antibody 17E6, applied to monolayer cultures of breast cancer lines, it was found that treatment of cells possessing detergent-insoluble (implying attachment to the actin cytoskeleton) E-cadherin resulted in the adoption of a spheroid configuration of cell growth. This effect was dependent upon not just alphav occupancy but also receptor aggregation. Thus in vitro alphav-dependent adhesion suppresses E-cadherin-mediated morphological changes. To investigate whether manipulation of E-cadherin would, conversely, modulate integrin activity we introduced a dominant-negative E-cadherin construct into one of the lines, ZR75-1, giving rise to the cell line ZR-E2R1. Surface expression of endogenous E-cadherin was downregulated (by around 25%), whereas beta-catenin levels were increased two- to threefold in ZR-E2R1 cells. There was also a highly significant increase in migration of ZR-E2R1 cells (relative to control cells) toward vitronectin (P<0.001), but not toward collagen type I, fibronectin or laminin. Such increased migration could be abrogated totally by antibody blockade of alphavbeta5 and alphavbeta1 integrins. There was no detectable change in alphav integrin levels. These data suggest that the introduction of a dominant-negative E-cadherin mutant into ZR75-1, in addition to a loss of cohesion, generates a signal (or signals) which increases migration towards vitronectin through increased activity of alphav integrins.

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