Interaction of human Thy-1 (CD 90) with the integrin αvβ3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium

Saalbach, Anja; Wetzel, Anne; Haustein, U.‐F.; Sticherling, Michael; Simon, Jan C.; Anderegg, Ulf

doi:10.1038/sj.onc.1208559

Cited by 87 publications

(96 citation statements)

References 47 publications

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“…In contrast, cell clones with reduced BMP4 expression or chordin overexpression ( Figure 3b) did not form tubes. It is further known that melanoma cells are able to interact with endothelial cells (Ding et al, 2005;Saalbach et al, 2005). So, we co-cultured melanoma and endothelial cells in matrigel and, indeed, co-cultures of Mel Im cells with HMEC resulted in tube formation (Figure 3c).…”

Section: Tube Formation Capacity Of Melanoma Cellsmentioning

confidence: 65%

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

et al. 2006

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Analyses of malignant melanomas revealed a strong expression of bone morphogenic proteins (BMPs) and their autocrine effect in promoting cell invasion and migration. Here, we report a paracrine effect of BMPs on the vascular network. Both BMP2 and BMP4 induced tube formation as well as the migratory efficiency of microvascular endothelial cells. Melanoma cells with reduced BMP activity attracted less endothelial cells in invasion assays than control cells. Furthermore, reduction of BMPs in melanoma cells had a strong effect on vasculogenic mimicry. Tube formation on matrigel was analysed for melanoma cells as well as in co-cultures of endothelial and melanoma cells. Melanoma cells with reduced BMP activity were not capable of forming cordlike structures by themselves and additionally inhibited tube formation of the endothelial cells. Genes involved in angiogenesis turned out to be strongly downregulated in these cell clones. Tumors derived from cells with impaired BMP activity showed reduced tumor growth or large necrotic areas owing to lack of angiogenesis in in vivo analyses.

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Section: Tube Formation Capacity Of Melanoma Cellsmentioning

confidence: 65%

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

et al. 2006

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“…Fibroblasts or activated HDMEC themselves did not produce MMP-9. Preincubation with a function-blocking anti-Thy-1 antibody (clone BC9; [24,25]) clearly decreased the MMP-9 secretion of neutrophils induced by interaction with activated HDMEC (Fig. 4A) as well as with fibroblasts (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Recently, we demonstrated that Thy-1 interacts with the b2-integrin Mac-1 [10] and the avb3-integrin [24]. Since avb3-integrin was hard to detect on neutrophils, we focused on the role of b2-integrins in the regulation of MMP-9 secretion.…”

Section: Discussionmentioning

confidence: 99%

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

et al. 2008

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Neutrophils are the first cells arriving at sites of acute inflammation. On their way from blood to the site of inflammation, neutrophils have to adhere to endothelial cells (EC), to transverse the basement membrane and subsequently to travel through the interstitial matrix. Recently, we have shown that human Thy-1 is an alternate EC receptor for the leukocyte integrin Mac-1 that contributes to leukocyte recruitment to sites of inflammation, providing a new pathway for adhesion and transmigration of neutrophils. Here, we studied the effect of Thy-1-mediated adhesion on neutrophil functions. Binding of neutrophils to recombinant human Thy-1 stimulated the release of MMP-9 from neutrophils, resulting in their enhanced migration through collagen-IV and matrigel. Further, we showed that neutrophil interaction with Thy-1 stimulated secretion of CXCL8 and thus could support the attraction of additional neutrophils to inflammatory sites. Blocking experiments confirmed the pivotal roles of Thy-1 on activated dermal EC or fibroblasts and its counter receptor CD18 on neutrophils for the regulation of MMP-9 and CXCL8 release from neutrophils. Our results support the general concept that the function of 'adhesion molecules' in particular of human Thy-1, may not only be to provide mechanical support but also regulate neutrophil functions.

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“…It is familiar to many investigators as a murine T cell marker. In contrast to rodents, CD90 is not expressed by human T cells and is only expressed by fibroblasts, myofibroblasts, neuronal cells, blood stem cells, and activated microvascular endothelial cells (35,(47)(48)(49). In the normal human intestinal mucosa, CD90 expression is mostly associated with myofibroblasts and fibroblasts (35,(47)(48)(49).…”

Section: Discussionmentioning

confidence: 95%

Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

Saada¹,

Pinchuk²,

Barrera³

et al. 2006

The Journal of Immunology

109

139

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The human gastrointestinal mucosa is exposed to a diverse normal microflora and dietary Ags and is a common site of entry for pathogens. The mucosal immune system must respond to these diverse signals with either the initiation of immunity or tolerance. APCs are important accessory cells that modulate T cell responses which initiate and maintain adaptive immunity. The ability of APCs to communicate with CD4+ T cells is largely dependent on the expression of class II MHC molecules by the APCs. Using immunohistochemistry, confocal microscopy, and flow cytometry, we demonstrate that α-smooth muscle actin+, CD90+ subepithelial myofibroblasts (stromal cells) constitutively express class II MHC molecules in normal colonic mucosa and that they are distinct from professional APCs such as macrophages and dendritic cells. Primary isolates of human colonic myofibroblasts (CMFs) cultured in vitro were able to stimulate allogeneic CD4+ T cell proliferation. This process was dependent on class II MHC and CD80/86 costimulatory molecule expression by the myofibroblasts. We also demonstrate that CMFs, engineered to express a specific DR4 allele, can process and present human serum albumin to a human serum albumin-specific and DR4 allele-restricted T cell hybridoma. These studies characterize a novel cell phenotype which, due to its strategic location and class II MHC expression, may be involved in capture of Ags that cross the epithelial barrier and present them to lamina propria CD4+ T cells. Thus, human CMFs may be important in regulating local immunity in the colon.

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Interaction of human Thy-1 (CD 90) with the integrin αvβ3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium

Cited by 87 publications

References 47 publications

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

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