Monocyte trans-endothelial migration augments subsequent transmigratory activity with increased PECAM-1 and decreased VE-cadherin at endothelial junctions

Hashimoto, Ken; Kataoka, Noriyuki; Nakamura, Emi; Hagihara, Kimiko; Hatano, Mizue; Okamoto, Takeaki; Kanouchi, Hiroaki; Minatogawa, Yohsuke; Mohri, Satoshi; Tsujioka, Katsuhiko; Kajiya, Fumihiko

doi:10.1016/j.ijcard.2010.12.018

Cited by 21 publications

(25 citation statements)

References 33 publications

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“…It is not clear from our results which monocyte-derived factors induce endothelial ICAM-1, but TNFa may be a candidate, as it is downregulated by adenosine treatment of monocytes (39). The effect of cell-cell interactions may also be important, as monocyte interaction with endothelial cells promotes subsequent transmigration due to CD31 accumulation at endothelial junctions (40).…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells from Colon Cancer Patients Inhibit Effector T-cell Migration through an Adenosine-Dependent Mechanism

Sundström

Stenstad

Langenes

et al. 2016

Cancer Immunology Research

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T cell-mediated immunity is a major component of antitumor immunity. In order to be efficient, effector T cells must leave the circulation and enter into the tumor tissue. Regulatory T cells (Treg) from gastric cancer patients, but not from healthy volunteers, potently inhibit migration of conventional T cells through activated endothelium. In this study, we compared T cells from colon cancer patients and healthy donors to determine the mechanisms used by Tregs from cancer patients to inhibit conventional T-cell migration. Our results showed that circulating Tregs from cancer patients expressed high levels of CD39, an ectoenzyme mediating hydrolysis of ATP to AMP, as a ratedetermining first step in the generation of immunosuppressive adenosine. Tumor-associated Tregs expressed even more CD39, and we therefore examined the importance of adenosine in Tregmediated inhibition of T-cell transendothelial migration in vitro. Exogenous adenosine significantly reduced migration of conventional T cells from healthy volunteers, and blocking either adenosine receptors or CD39 enzymatic activity during transmigration restored the ability of conventional T cells from cancer patients to migrate. Adenosine did not directly affect T cells or endothelial cells, but reduced the ability of monocytes to activate the endothelium. Taken together, our results indicate that Treg-derived adenosine acts on monocytes and contributes to reduced transendothelial migration of effector T cells into tumors. This effect of Tregs is specific for cancer patients, and our results indicate that Tregs may affect not only T-cell effector functions but also their migration into tumors.

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Section: Discussionmentioning

confidence: 99%

Regulatory T Cells from Colon Cancer Patients Inhibit Effector T-cell Migration through an Adenosine-Dependent Mechanism

Sundström

Stenstad

Langenes

et al. 2016

Cancer Immunology Research

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“…Various endogenous (cytokines) or microbial substances can activate the endothelium locally [19]. This activation of the endothelium results in adhesion and transmigration of white blood cells such as neutrophils, monocytes, macrophages, and T-cells into the underlying tissue and help there to fight the infection [133,[136][137][138]. In turn, this transmigration process left the endothelium as well as the white blood cells in an activated state.…”

Section: Cell-layers Are a Barrier For Cell Invasion (Old Role)mentioning

confidence: 99%

“…In turn, this transmigration process left the endothelium as well as the white blood cells in an activated state. Furthermore, the sprouting of new blood vessels that originate from existing blood vessels is facilitated by endothelial cells-called angiogenesis [137]. There are three fundamentally different types of endothelium: continuous, fenestrated, and discontinuous endothelium.…”

Section: Cell-layers Are a Barrier For Cell Invasion (Old Role)mentioning

confidence: 99%

The Biomechanical Properties of 3d Extracellular Matrices and Embedded Cells Regulate the Invasiveness of Cancer Cells

Mierke

2011

Cell Biochem Biophys

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The malignancy of tumors depends on the biomechanical properties of cancer cells and their microenvironment, which enable cancer cells to migrate through the connective tissue, transmigrate through basement membranes and endothelial monolayers and form metastases in targeted organs. The current focus of cancer research is still based on biological capabilities such as molecular genetics and gene signaling, but these approaches ignore the mechanical nature of the invasion process of cancer cells. This review will focus on how structural, biochemical and mechanical properties of extracellular matrices (ECMs), and adjacent cells regulate the invasiveness of cancer cells. In addition, it presents how cancer cells create their own microenvironment by restructuring of the ECM and by interaction with stromal cells, which then further contribute to the progression of cancer disease. Finally, this review will point out that mechanical properties are a critical determinant for the efficiency of cancer cell invasion and the progression of cancer which might affect the future development of new cancer treatments.

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“…A PECAM-1-GFP vector, in which Aequorea coerulescens-derived GFP (AcGFP1) was fused with the intracellular C-terminus of PECAM-1, was constructed, and the proper expression and intracellular location of the fusion protein was confirmed as reported elsewhere [8,13]. Transient transfection of PECAM-1-GFP into HUVECs was performed by use of nucleofector (Lonza, Switzerland), and the transfectant was seeded on to 35-mm glassbottomed dishes (cover glass / = 12 mm; Asahi glass, Japan) coated with fibronectin (4 lg/cm 2 ).…”

Section: Molecular Imaging Of Pecam-1 During Monocyte Trans-cellular mentioning

confidence: 97%

“…A large number of molecules at endothelial junctions have been implicated in the former, including platelet-endothelial cell adhesion molecule-1 (PECAM-1) [6][7][8][9][10], vascular endothelial cadherin (VE-cadherin) [7], and junctional adhesion molecules (JAMs) [11]. We have previously described a live-cell imaging system for monocyte trans-endothelial migration [12], and demonstrated that oxidized LDL [7] or monocyte para-cellular migration [13] alters endothelial junctional organization, increasing PECAM-1 and reducing VE-cadherin, which results in enhanced transmigratory activity.…”

Section: Introductionmentioning

confidence: 99%

Live-cell visualization of the trans-cellular mode of monocyte transmigration across the vascular endothelium, and its relationship with endothelial PECAM-1

et al. 2011

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In response to atherogenic stimuli, blood monocytes transmigrate across the vascular endothelium not only through endothelial cell-cell junctions (para-cellular) but also through endothelial cells themselves (trans-cellular). The molecular mechanism of the latter is mostly unknown, because it rarely happens, especially in vitro. Although many reports have recognized trans-cellular migration from snapshot images of leukocytes halfway across the endothelium at non-junctional locations, it often produces a false-positive result, because some leukocytes that initiate trans-cellular migration withdraw and return to the apical endothelial surface. Thus, analyzing the entire process is essential. In this study, complete monocyte trans-cellular migration was successfully captured for live cells, with simultaneous visualization of endothelial PECAM-1. We suggest the possible existence of both PECAM-1-related migration at peri-junctional sites and PECAM-1-unrelated migration at sites remote from junctions. This is the first report to describe the entire process of monocyte trans-cellular migration for live cells and its relationship with endothelial PECAM-1.

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Monocyte trans-endothelial migration augments subsequent transmigratory activity with increased PECAM-1 and decreased VE-cadherin at endothelial junctions

Cited by 21 publications

References 33 publications

Regulatory T Cells from Colon Cancer Patients Inhibit Effector T-cell Migration through an Adenosine-Dependent Mechanism

Regulatory T Cells from Colon Cancer Patients Inhibit Effector T-cell Migration through an Adenosine-Dependent Mechanism

The Biomechanical Properties of 3d Extracellular Matrices and Embedded Cells Regulate the Invasiveness of Cancer Cells

Live-cell visualization of the trans-cellular mode of monocyte transmigration across the vascular endothelium, and its relationship with endothelial PECAM-1

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