Influence of stress on extracellular matrix and integrin biology

Jean, Christine; Gravelle, Pauline; Fournié, Jean Jacques; Laurent, Guy

doi:10.1038/onc.2011.27

Cited by 88 publications

(77 citation statements)

References 118 publications

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“…Integrin, a heterodimeric transmembrane receptor composed of α-and β-subunits, has a fundamental role in communication between cells and the extracellular matrix [1,2]. Recent studies have shown that trafficking of integrin is a crucial step in this communication [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking

Lee

Kim

2014

Eur J Immunol

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Integrin trafficking, including internalization, recycling, and lysosomal degradation, is crucial for the regulation of cellular functions. Exosomes, nano-sized extracellular vesicles, are believed to play important roles in intercellular communications. This study demonstrates that exosomes released from human macrophages negatively regulate endothelial cell migration through control of integrin trafficking. Macrophage-derived exosomes promote internalization of integrin β1 in primary HUVECs. The internalized integrin β1 persistently accumulates in the perinuclear region and is not recycled back to the plasma membrane. Experimental results indicate that macrophage-derived exosomes stimulate trafficking of internalized integrin β1 to lysosomal compartments with a corresponding decrease in the integrin destined for recycling endosomes, resulting in proteolytic degradation of the integrin. Moreover, ubiquitination of HUVEC integrin β1 is enhanced by the exosomes, and exosome-mediated integrin degradation is blocked by bafilomycin A, a lysosomal degradation inhibitor. Macrophage-derived exosomes were also shown to effectively suppress collagen-induced activation of the mitogenactivated protein kinase/extracellular signal-regulated kinase signaling pathway and HUVEC migration, which are both dependent on integrin β1. These observations provide new insight into the functional significance of exosomes in the regulation of integrin trafficking. Keywords: Endothelial cell migration r Exosomes r Integrin trafficking r MacrophagesAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionIntegrin, a heterodimeric transmembrane receptor composed of α-and β-subunits, has a fundamental role in communication between cells and the extracellular matrix [1,2]. Recent studies have shown that trafficking of integrin is a crucial step in this communication [3][4][5]. Integrin is regularly internalized via the endocytosis pathway and internalized integrin is recycled back to the plasma membrane [3,4]. Internalized integrin β1, the most widely expressed integrin subunit, accumulates in the perinuclear Correspondence: Dr. Doo-Sik Kim e-mail: dskim@yonsei.ac.kr region of cells and is returned to the plasma membrane through RAB11-positive recycling endosomes [3]. The recycling process rearranges the distribution of integrins on the cell surface and controls the direction of cell migration [3]. Ubiquitination of integrin acts as a signal to trigger trafficking of internalized integrin to the lysosomal degradation compartment [5,6]. The degradation process is important for controlling the proper expression level of integrin on the cell surface, by which cell-matrix association and cell migration are tightly regulated [5,7].Integrin is a key regulator of cellular functions associated with vascular processes [8,9]. Endothelial cell migration and leukocyte recruitment during inflammation are tightly controlled by integrin functions. The expression and activation of integrins C...

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Section: Introductionmentioning

confidence: 99%

Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking

Lee

Kim

2014

Eur J Immunol

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“…It is a complex assembly of many proteins such as fibrous structural proteins and proteoglycans, forming an elaborate network within tissues [1,2]. ECM is not only a simple static scaffold, but also can be modified through remodeling to create an environment for tumor metastasis [3].…”

Section: Introductionmentioning

confidence: 99%

Role of Integrins in Regulating Proteases to Mediate Extracellular Matrix Remodeling

Yue

Zhang

Chen

2012

Cancer Microenvironment

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The extracellular matrix (ECM) is an extracellular scaffold composed of complex mixtures of proteins that plays a pivotal role in tumor progression. ECM remodeling is crucial for tumor migration and invasion during the process of metastasis. ECM can be remodeled by several processes including synthesis, contraction and proteolytic degradation. In order to cross through the ECM barriers, malignant cells produce a spectrum of extracellular proteinases including matrix metalloproteinases (MMPs), serine proteases (mainly the urokinase plasminogen activator (uPA) system) and cysteine proteases to degrade ECM components. As major adhesion molecules to support cell attachment to ECM, integrins play critical roles in tumor progression by enhancing tumor cell survival, migration and invasion. Previous studies have shown that integrins can regulate the expression and activity of these proteases through different pathways. This review summarizes the roles of MMPs and uPA system in ECM remodeling and discusses the regulatory functions of integrins on these proteases in invasive tumors.

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“…Beyond this role, cell-ECM adhesion promotes various intracellular signalling pathways and effectors modulating cell survival or apoptosis and tumor growth (Geiger & Yamada, 2011). Cells use a number of different cell surface receptors that mediate cell-ECM adhesion, being one of the best studied the integrins (Jean et al, 2011;Schwartz, 2010). It is known that binding of integrins to their ligands is dependent on the presence of divalent cations including Ca 2+ , Mg 2+ , and Mn 2+ (CierniewskaCieslak et al, 2002;Cluzel et al, 2005;Leitinger et al, 2000;Luo & Springer, 2006).…”

Section: Introductionmentioning

confidence: 99%

Integrin-Mediated Endothelial Cell Adhesion and Activation of c-Src, EGFR and ErbB2 are Required for Endothelial-Mesenchymal Transition

Arciniegas¹,

Carrillo²,

Rojas³

et al. 2011

Pulmonary Hypertension - From Bench Research to Clinical Challenges

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Influence of stress on extracellular matrix and integrin biology

Cited by 88 publications

References 118 publications

Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking

Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking

Role of Integrins in Regulating Proteases to Mediate Extracellular Matrix Remodeling

Integrin-Mediated Endothelial Cell Adhesion and Activation of c-Src, EGFR and ErbB2 are Required for Endothelial-Mesenchymal Transition

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