Molecular Isolation and Characterization of a Soluble Isoform of Activated Leukocyte Cell Adhesion Molecule That Modulates Endothelial Cell Function

Ikeda, Koji; Quertermous, Thomas

doi:10.1074/jbc.m407776200

Cited by 80 publications

(80 citation statements)

References 34 publications

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“…2A, right), confirming protein expression and secretion. The double bands on the Western blot were due to two N-linked glycosylation sites in sALCAM (20). It was noticed in the course of the experiments that BLM/sA high clones tended to completely lose sALCAM expression.…”

Section: Resultsmentioning

confidence: 90%

“…The recent isolation of an alternative transcript encoding a secreted sALCAM variant in endothelial cells hinted at a novel regulatory mechanism of ALCAM (20). Therefore, we determined if sALCAM transcripts were present in the human melanoma cell line BLM.…”

Section: Resultsmentioning

confidence: 99%

“…Soluble ALCAM variants and anti-ALCAM antibodies inhibited the trans-endothelial migration of monocytes but did not affect their migration or adhesion to endothelium. Ectopic ALCAM overexpression generally promoted cell-cell interactions (14,20), whereas soluble, recombinant ALCAM variants attenuated cell-cell interactions (refs. 20, 46; this report).…”

Section: Discussionmentioning

confidence: 99%

“…1C). The sALCAM variant, which apparently impaired cell-cell interactions, was recently isolated as an alternative, shortened ALCAM transcript in endothelial cells (20). This transcript comprised the first three exons and only encoded the NH 2 -terminal signal sequence plus immunoglobulin domain D1.…”

Section: Introductionmentioning

confidence: 99%

“…Immunoglobulin domain D1 was required for ligand binding (14). Exposure of endothelial cells to recombinant sALCAM increased cell migration and decreased capillary tube formation (20). We thus anticipated that transfection of sALCAM into metastatic melanoma cells would influence cell clustering by challenging ligand-receptor binding and intercellular network formation of endogenous ALCAM (cf.…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of Melanoma Invasion by a Secreted Variant of Activated Leukocyte Cell Adhesion Molecule

et al. 2008

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Activated leukocyte cell adhesion molecule (ALCAM/CD166/ MEMD), a marker of various cancers and mesenchymal stem cells, is involved in melanoma metastasis. We have exploited a secreted NH 2 -terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration. Overexpression of sALCAM in metastatic melanoma cells disturbed clustering of endogenous ALCAM and inhibited activation of matrix metalloproteinase-2 (MMP-2). Exposure of HT1080 fibrosarcoma cells to sALCAM similarly inhibited MMP-2, suggesting a broader effect on ALCAMpositive tumor cells. In contrast to the previously reported, promotive effects of an NH 2 -terminally truncated, transmembrane variant (#N-ALCAM), sALCAM impaired the migratory capacity of transfected cells in vitro, reduced basement membrane penetration in reconstituted human skin equivalents, and diminished metastatic capacity in nude mice. Remarkably, L1 neuronal cell adhesion molecule (L1CAM/ CD171), another progression marker of several cancers including melanoma, was suppressed upon sALCAM overexpression but was up-regulated by #N-ALCAM. The partially overlapping and opposite effects induced by alternative strategies targeting ALCAM functions collectively attribute an integrative role to ALCAM in orchestrating cell adhesion, growth, invasion, and proteolysis in the tumor tissue microenvironment and disclose a therapeutic potential for sALCAM. [Cancer Res 2008;68(10):3671-9]

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Attenuation of Melanoma Invasion by a Secreted Variant of Activated Leukocyte Cell Adhesion Molecule

et al. 2008

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Inflammation, Immunology and Allergy

Steinhoff

2016

Rook's Textbook of Dermatology, Ninth Edition

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Inflammation can be defined as a complex body defence mechanism responding to dangerous endogenous or exogenous stimuli in order to restore body homeostasis. Thus, the skin is continuously challenged to prevent inflammation, and inflammatory skin diseases are very common worldwide. Similarly, allergic reactions (types 1–4) are inflammatory processes created by the body system to respond to ‘danger signals’ of various origins. Very early in phylogenesis, inflammation is associated with the host defence against infectious, allergic or toxic agents, UV radiation, noxious heat and cold, or other injury. Innate and later adaptive immune mechanisms have been established that, uncontrolled, potentially lead to chronic disease or death, as in anaphylactic shock. The body system responds with the induction of various inflammatory pathways such as radical oxygen species, nitric oxide derivatives, complement compounds, adenosine monophosphate, antimicrobial peptides, cytokines, chemokines, prostaglandins, leukotrienes, proteases, neuropeptides and growth factors, just to name a few. This chapter systematically covers the various mechanisms that regulate inflammatory and allergic responses and refers in a translational setting to the diseases that are involved in order better to understand the clinical characteristics of a skin disease, its differential diagnoses and optimal treatment options.

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