scholarly journals Involvement of Integrin αvβ3and Cell Adhesion Molecule L1 in Transendothelial Migration of Melanoma Cells

2001 ◽  
Vol 12 (9) ◽  
pp. 2699-2710 ◽  
Author(s):  
Evelyn B. Voura ◽  
Ravi A. Ramjeesingh ◽  
Anthony M.P. Montgomery ◽  
Chi-Hung Siu
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Polyclonal Antibodies ◽  
Transendothelial Migration ◽  
Melanoma Cells ◽  
Vitro Assay ◽  
Adhesive Interactions

Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin αvβ3, has been associated with the metastatic potential of tumor cells. In this study, we used a novel in vitro assay to examine the role of αvβ3 in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin αvβ3 on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. αvβ3 was also enriched in heterotypic contacts between endothelial cells and melanoma cells. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-αvβ3monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin αvβ3, only L1 serves as a potential ligand for αvβ3 during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and αvβ3 antibodies did not show additive effects, suggesting that they are components of the same adhesion system. Together, the data suggest that interactions between the integrin αvβ3 on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.

scholarly journals Transendothelial Migration of Melanoma Cells Involves N-Cadherin-mediated Adhesion and Activation of the β-Catenin Signaling Pathway

2005 ◽  
Vol 16 (9) ◽  
pp. 4386-4397 ◽  
Author(s):  
Jianfei Qi ◽  
Ning Chen ◽  
Junfu Wang ◽  
Chi-Hung Siu
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Transendothelial Migration ◽  
Melanoma Cells ◽  
Dominant Negative ◽  
Vitro Assay ◽  
Multistep Process ◽  
Adhesive Interactions

Cancer metastasis is a multistep process involving many types of cell-cell interactions, but little is known about the adhesive interactions and signaling events during extravasation of cancer cells. Transendothelial migration of cancer cells was investigated using an in vitro assay, in which melanoma cells were seeded on top of a monolayer of endothelial cells. Attachment of melanoma cells on the endothelium induced a twofold increase in N-cadherin expression in melanoma cells and the redistribution of N-cadherin to the heterotypic contacts. Transendothelial migration was inhibited when N-cadherin expression was repressed by antisense RNA, indicating a key role played by N-cadherin. Whereas N-cadherin and β-catenin colocalized in the contact regions between melanoma cells and endothelial cells during the initial stages of attachment, β-catenin disappeared from the heterotypic contacts during transmigration of melanoma cells. Immunolocalization and immunoprecipitation studies indicate that N-cadherin became tyrosine-phosphorylated, resulting in the dissociation of β-catenin from these contact regions. Concomitantly, an increase in the nuclear level of β-catenin occurred in melanoma cells, together with a sixfold increase in β-catenin-dependent transcription. Transendothelial migration was compromised in cells expressing a dominant-negative form of β-catenin, thus supporting a regulatory role of β-catenin signaling in this process.

scholarly journals Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV

2006 ◽  
Vol 80 (23) ◽  
pp. 11539-11555 ◽  
Author(s):  
Gretchen L. Bentz ◽  
Marta Jarquin-Pardo ◽  
Gary Chan ◽  
M. Shane Smith ◽  
Christian Sinzger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Human Cytomegalovirus ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Hcmv Infection ◽  
Transendothelial Migration ◽  
Fiber Formation ◽  
Cell Adhesion Molecule 1

ABSTRACT Human cytomegalovirus (HCMV) pathogenesis is dependent on the hematogenous spread of the virus to host tissue. While data suggest that infected monocytes are required for viral dissemination from the blood to the host organs, infected endothelial cells are also thought to contribute to this key step in viral pathogenesis. We show here that HCMV infection of endothelial cells increased the recruitment and transendothelial migration of monocytes. Infection of endothelial cells promoted the increased surface expression of cell adhesion molecules (intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and platelet endothelial cell adhesion molecule 1), which were necessary for the recruitment of naïve monocytes to the apical surface of the endothelium and for the migration of these monocytes through the endothelial cell layer. As a mechanism to account for the increased monocyte migration, we showed that HCMV infection of endothelial cells increased the permeability of the endothelium. The cellular changes contributing to the increased permeability and increased naïve monocyte transendothelial migration include the disruption of actin stress fiber formation and the decreased expression of lateral junction proteins (occludin and vascular endothelial cadherin). Finally, we showed that the migrating monocytes were productively infected with the virus, documenting that the virus was transferred to the migrating monocyte during passage through the lateral junctions. Together, our results provide evidence for an active role of the infected endothelium in HCMV dissemination and pathogenesis.

scholarly journals A Direct Interaction of Axonin-1 with Ngcam-Related Cell Adhesion Molecule (Nrcam) Results in Guidance, but Not Growth of Commissural Axons

2000 ◽  
Vol 149 (4) ◽  
pp. 951-968 ◽  
Author(s):  
Dora Fitzli ◽  
Esther T. Stoeckli ◽  
Stefan Kunz ◽  
Kingsley Siribour ◽  
Christoph Rader ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Direct Interaction ◽  
Longitudinal Axis ◽  
Vitro Assay ◽  
Commissural Axons ◽  
Related Cell

An interaction of growth cone axonin-1 with the floor-plate NgCAM-related cell adhesion molecule (NrCAM) was shown to play a crucial role in commissural axon guidance across the midline of the spinal cord. We now provide evidence that axonin-1 mediates a guidance signal without promoting axon elongation. In an in vitro assay, commissural axons grew preferentially on stripes coated with a mixture of NrCAM and NgCAM. This preference was abolished in the presence of anti–axonin-1 antibodies without a decrease in neurite length. Consistent with these findings, commissural axons in vivo only fail to extend along the longitudinal axis when both NrCAM and NgCAM interactions, but not when axonin-1 and NrCAM or axonin-1 and NgCAM interactions, are perturbed. Thus, we conclude that axonin-1 is involved in guidance of commissural axons without promoting their growth.

scholarly journals Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo

1997 ◽  
Vol 185 (7) ◽  
pp. 1349-1358 ◽  
Author(s):  
Fang Liao ◽  
Jahanara Ali ◽  
Tricia Greene ◽  
William A. Muller
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Transendothelial Migration ◽  
Endothelial Cell Adhesion Molecule ◽  
Platelet Endothelial Cell Adhesion ◽  
Endothelial Cell Adhesion

The inflammatory response involves sequential adhesive interactions between cell adhesion molecules of leukocytes and the endothelium. Unlike the several adhesive steps that precede it, transendothelial migration (diapedesis), the step in which leukocytes migrate between apposed endothelial cells, appears to involve primarily one adhesion molecule, platelet–endothelial cell adhesion molecule (PECAM, CD31). Therefore, we have focused on PECAM as a target for antiinflammatory therapy. We demonstrate that soluble chimeras made of the entire extracellular portion of PECAM, or of only the first immunoglobulin domain of PECAM, fused to the Fc portion of IgG, block diapedesis in vitro and in vivo. Furthermore, the truncated form of the PECAM-IgG chimera does not bind stably to its cellular ligand. This raises the possibility of selective anti-PECAM therapies that would not have the untoward opsonic or cell-activating properties of antibodies directed against PECAM.

scholarly journals Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1.

1992 ◽  
Vol 176 (1) ◽  
pp. 99-107 ◽  
Author(s):  
L Osborn ◽  
C Vassallo ◽  
C D Benjamin
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Binding Sites ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Vascular cell adhesion molecule-1 (VCAM-1) is induced on endothelial cells by inflammatory cytokines, and binds mononuclear leukocytes through the integrin very late antigen-4 (VLA-4) (alpha 4 beta 1). This adhesion pathway has been implicated in a diverse group of physiological and pathological processes, including B cell development, leukocyte activation and recruitment to sites of inflammation, atherosclerosis, and tumor cell metastasis. The major form of VCAM-1 (VCAM-7D) has seven extracellular immunoglobulin (Ig)-like domains, of which the three NH2-terminal domains (domains 1-3) are similar in amino acid sequence to domains 4-6. By functional analysis of VCAM-7D relative to VCAM-6D (a minor 6-domain form of VCAM-1 in which domain 4 is deleted because of alternative splicing), and chimeric constructs between VCAM-1 and its structural relative intercellular adhesion molecule-1 (ICAM-1), we show that either the first or the homologous fourth domain of VCAM-1 is required for VLA-4-dependent adhesion. Either of these binding sites can function in the absence of the other. When both are present, cell binding activity is increased relative to monovalent forms of the molecule. The homologous binding regions appear to have originated by internal duplication of a portion of a monovalent ancestral gene, before the mammalian radiation. Thus VCAM-1 exemplifies evolution of a functionally bivalent cell-cell adhesion molecule by intergenic duplication. We have also produced a new class of anti-VCAM-1 monoclonal antibodies that block domain 4-dependent adhesion, and demonstrate that both binding sites participate in the adhesion function of VCAM-1 on endothelial cells in vitro. Therefore both sites must be blocked in clinical, animal, or in vitro studies depending on the use of anti-VCAM-1 antibodies to inactivate the VCAM-1/VLA-4 adhesion pathway.

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