Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix

Wu, Chuanyue; Keivens, V. M.; O’Toole, Timothy E.; McDonald, John A.; Ginsberg, Mark H.

doi:10.1016/0092-8674(95)90184-1

Cited by 330 publications

(317 citation statements)

References 67 publications

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“…Type I collagen assembles passively into matrix by self-polymerization (32), although certain proteins, including other collagen types, fibromodulin, lumican, decorin, and tenascin, can modify this process (33)(34)(35). In contrast, fibronectin matrix assembly is an active process and requires several conditions: an intact intracellular cytoskeleton, an activated fibronectin-binding integrin receptor, and tension across the developing fibrillar structure (36,37). Investigators in our group showed previously that TGF␤ and PDGF stimulate fibronectin matrix assembly, possibly through changes in integrin receptor activity (29).…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Kissin¹,

Lemaire²,

Korn³

et al. 2002

Arthritis & Rheumatism

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Objective. Fibrillin, an extracellular matrix protein implicated in dermal fibrosis, is increased in the reticular dermis of systemic sclerosis (SSc) skin. We undertook this study to investigate the hypothesis that transforming growth factor ␤ (TGF␤) or other cytokines regulate fibrillin matrix formation by normal and SSc fibroblasts. We further investigated the mechanism of TGF␤-induced fibrillin fibrillogenesis and its relationship to myofibroblasts.Methods. Fibrillin and fibronectin matrix deposition and ␣-smooth muscle actin expression by fibroblast cultures from normal and SSc skin treated with TGF␤ or other cytokines were analyzed by immunofluorescence. Supernatant and extracellular matrix from normal and SSc fibroblasts treated with or without TGF␤ were evaluated by Western blot and Northern blot for fibrillin protein and messenger RNA (mRNA) expression, respectively.Results. Immunofluorescence demonstrated increased fibrillin matrix formation by normal and scleroderma fibroblasts after TGF␤ treatment. Other cytokines, including tumor necrosis factor ␣, interleukin-1␤ (IL-1␤), IL-4, granulocyte-macrophage colonystimulating factor, and platelet-derived growth factor, did not affect fibrillin fibrillogenesis. Fibrillin matrix formed in proximity to myofibroblasts and independently of up-regulation of fibronectin matrix or cell number. Western blot analysis of extracellular matrix confirmed increased fibrillin after TGF␤ stimulation of normal or scleroderma fibroblasts. However, TGF␤ did not alter the expression of either soluble fibrillin protein or fibrillin mRNA.Conclusion. Our data show that TGF␤ induces fibrillin protein incorporation into the extracellular matrix without affecting fibrillin gene expression or protein synthesis, suggesting that fibrillin matrix assembly is regulated extracellularly. TGF␤ might increase fibrillin matrix by activating myofibroblasts. Such TGF␤-mediated effects could account for the increased fibrillin matrix observed in SSc skin.

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Section: Discussionmentioning

confidence: 99%

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Kissin¹,

Lemaire²,

Korn³

et al. 2002

Arthritis & Rheumatism

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“…To account for the possibility that FN added to cell-free ECMs may not be properly incorporated into the matrices, we also added FN to 3D fibroblast cultures during the ECM production stage. Other investigators 11,33 showed that mammalian cells are capable of incorporating exogenously supplied FN into their ECMs. The addition of FN in this manner indeed increased the ECM FN content ( Figure 6B, right) without changing the fiber architecture (data not shown).…”

Section: Increased Fn Content In Ecm-sdc1 Promotes Breast Carcinoma Cmentioning

confidence: 99%

Syndecan-1 in Breast Cancer Stroma Fibroblasts Regulates Extracellular Matrix Fiber Organization and Carcinoma Cell Motility

Yang

Mosher

Seo

et al. 2011

The American Journal of Pathology

123

126

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Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1). In human breast carcinoma samples, stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture. To examine a possible link between stromal Sdc1 and the fiber architecture, we generated bioactive cell-free three-dimensional ECMs from cultures of Sdc1-positive and Sdc1-negative murine and human mammary fibroblasts (termed ECM-Sdc1 and ECM-mock, respectively). Indeed, ECM-Sdc1 showed a parallel fiber architecture that contrasted markedly with the random fiber arrangement of ECM-mock. When breast carcinoma cells were seeded into the fibroblast-free ECMs, ECM-Sdc1, but not ECM-mock, promoted their attachment, invasion, and directional movement. We further evaluated the contribution of the structural/compositional modifications in ECM-Sdc1 on carcinoma cell behavior. By microcontact printing of culture surfaces, we forced the Sdc1-negative fibroblasts to produce ECM with parallel fiber organization, mimicking the architecture observed in ECM-Sdc1. We found that the fiber topography governs carcinoma cell migration directionality. Conversely, an elevated fibronectin level in ECM-Sdc1 was responsible for the enhanced attachment of the breast carcinoma cells. These observations suggest that Sdc1 expression in breast carcinoma stromal fibroblasts promotes the assembly of an architecturally abnormal ECM that is permissive to breast carcinoma directional migration and invasion. Epithelial-stromal interactions play crucial roles in directing mammary gland development and in maintaining normal tissue homeostasis. Conversely, during tumorigenesis, the stroma accelerates carcinoma growth and progression. The predominant cell type within the stromal compartment is the fibroblast, which synthesizes, organizes, and maintains a three-dimensional (3D) network of glycoproteins and proteoglycans known as the extracellular matrix (ECM). Normal stromal fibroblasts and their ECM are believed to exert an inhibitory constraint on tumor growth and progression. 1,2 Major alterations occur in the stromal fibroblasts and ECM during neoplastic transformation, giving rise to a permissive and supportive microenvironment for carcinomas. Compared with their quiescent normal counterpart, carcinoma-associated fibroblasts display an activated phenotype, which is characterized by the expression of smooth muscle markers, an enhanced proliferative and migratory potential, and altered gene expression profiles. Carcinoma-associated fibroblasts produce and deposit elevated amounts and abnormal varieties of ECM components. 3-5 Recent evidence 6,7 indicates that not only ECM composition but also ECM architecture are altered in carcinomas and that these changes may promote tumor progression. However, the contribution of these stromal modifications to tumor development and the molecular mechanisms and signaling events underlying these alterations are incompletely understood.

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“…Fibrillins have ArgGly-Asp (RGD) sequences that interact with integrins (Pfaff et al, 1996;Sakamoto et al, 1996;Bax et al, 2003) and heparin-binding domains that interact with cell surface heparan sulfate proteoglycans (Tiedemann et al, 2001;Ritty et al, 2003), suggesting that fibrillins directly signal cells through these receptors. Furthermore, in vivo assembly of fibrillin may require cell-surface receptors in a similar manner to fibronectin (Wu et al, 1995). Fibrillins also have a major role in binding and sequestering growth factors, such as TGF-b, into the ECM (Neptune et al, 2003).…”

Section: Fibrillinsmentioning

confidence: 99%

New insights into elastic fiber assembly

Wagenseil

Mecham

2007

Birth Defects Research Pt C

355

354

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Elastic fibers provide recoil to tissues that undergo repeated stretch, such as the large arteries and lung. These large extracellular matrix (ECM) structures contain numerous components, and our understanding of elastic fiber assembly is changing as we learn more about the various molecules associated with the assembly process. The main components of elastic fibers are elastin and microfibrils. Elastin makes up the bulk of the mature fiber and is encoded by a single gene. Microfibrils consist mainly of fibrillin, but also contain or associate with proteins such as microfibril associated glycoproteins (MAGPs), fibulins, and EMILIN-1. Microfibrils were thought to facilitate alignment of elastin monomers prior to cross-linking by lysyl oxidase (LOX). We now know that their role, as well as the overall assembly process, is more complex. Elastic fiber formation involves elaborate spatial and temporal regulation of all of the involved proteins and is difficult to recapitulate in adult tissues. This report summarizes the known interactions between elastin and the microfibrillar proteins and their role in elastic fiber assembly based on in vitro studies and evidence from knockout mice. We also propose a model of elastic fiber assembly based on the current data that incorporates interactions between elastin, LOXs, fibulins and the microfibril, as well as the pivotal role played by cells in structuring the final functional fiber. Birth Defects Research (Part C) 81:229-240,

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Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix

Cited by 330 publications

References 67 publications

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Syndecan-1 in Breast Cancer Stroma Fibroblasts Regulates Extracellular Matrix Fiber Organization and Carcinoma Cell Motility

New insights into elastic fiber assembly

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