CD146 (MUC18/MCAM): An activation antigen of human T lymphocytes

Pickl, Winfried F.; Majdic, Otto; Fischer, Gottfried; Petzelbauer, Peter; Faé, Ingrid; Waclavicek, Martina; Stöckl, Johannes; Scheinecker, Clemens; Vidicki, T; Aschauer, H; Johnson, Judith P.; Knapp, Walter

doi:10.1016/s0165-2478(97)85808-7

Cited by 14 publications

(12 citation statements)

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“…However, the expression by T cell lines is in keeping with a recent report that MUC18 is expressed on activated T cells. 30 Our findings are reinforced by the detection of MUC18 on cells from patients with acute leukemia of lymphoid (T or B) or myeloid lineage, as well as some with chronic B cell lymphoproliferative disorders. The cells tested came from patients of various ages and at different stages of disease progression.…”

Section: Figuresupporting

confidence: 60%

“…19 While early studies suggested a lack of expression on normal peripheral blood lymphocytes or human leukemic cell lines, 18 MUC18 has recently been recognized as an activation antigen on human T lymphocytes. 30 In addition to cloning data, we were able to immunoprecipitate a 100-110 kDa protein from the pre-B cell line NALM-6 which is comparable to the 113 kDa protein of MUC18 precipitated from a melanoma cell line. 29 This suggests that the mature protein exists in a glycosylated form, as is the case for other members of the IgSF such as VCAM-1 13 and NCAM.…”

Section: Figurementioning

confidence: 68%

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MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies

et al. 1998

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Despite the importance of bone marrow stromal cells in hemopoiesis, the profile of surface molecule expression is relatively poorly understood. Mice were immunized with cultured human bone marrow stromal cells in order to raise monoclonal antibodies to novel cell surface molecules, which might be involved in interactions with hemopoietic cells. Three antibodies, WM85, CC9 and EB4 were produced, and were found to identify a 100-110 kDa antigen on bone marrow fibroblasts.

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Section: Figuresupporting

confidence: 60%

Section: Figurementioning

confidence: 68%

MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies

et al. 1998

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“…MUC18-mediated adhesion between melanoma cells and endothelial cells, via an unknown heterophilic ligand, may be important for the movement of melanoma cells in and out of the tumor vasculature [34,47,50,59]. Activated peripheral T lymphocytes also express MUC18, with an increased capacity to bind endothelial cells that contributes to T-cell extravasation and/or homing [10,40,44]. Overall these observations indicate that interactions between MUC18-positive tumor cells and endothelial cells (and activated T-lymphocytes), may play an important role in (cutaneous and uveal) melanoma hematogenous spread and immunoregulation.…”

Section: Discussionmentioning

confidence: 99%

Expression and distribution of MUC18 in human uveal melanoma

et al. 2007

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The immunoglobulin superfamily protein MUC18 is involved in transendothelial migration and signal transduction, and is expressed in malignancies including cutaneous melanoma. Recent in vitro studies showed evidence of increased MUC18 protein in some uveal melanoma cell lines with an increased potential for invasion. We assessed seven uveal and three metastasis-derived melanoma cell lines for the expression of MUC18 mRNA and protein by RT-PCR, and immunoblotting and immunocytochemistry, respectively. We also examined the expression and distribution of MUC18 in paraffin sections of primary uveal melanomas (n = 23; 5/23 spindle; 18/23 mixed and epithelioid) and normal eyes (n = 3) using a polyclonal goat anti-human antibody to MUC18 visualized with peroxidase and Vector NovaRED. Distribution and intensity of immunostaining was graded semi-quantitatively (grade 0 to 3) by 2 independent observers. All cell lines expressed MUC18 mRNA and protein ( approximately 130 kDa), and showed punctate cell membrane MUC18 immunostaining. Primary melanomas displayed heterogeneous cell membrane and cytoplasmic MUC18, with moderate to strong immunolabelling (> or =grade 2) in approximately 70% of tumours. Vasculature in tumours and in retina and choroid of all melanoma-affected and normal eyes showed intense MUC18 immunostaining. These observations further suggest a role for MUC18 in uveal melanoma growth; moreover, interactions between MUC18-positive melanoma cells and vasculature may be important for the hematogenous spread of cells during metastases.

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“…Melanoma cells seeded at clonal cell densities show poor survival and growth in growth factor-depleted medium (unpublished observation), suggesting that cell ± cell adhesion provides the cells with a major survival and growth advantage. Mel-CAM has also been detected on activated T cells (Pickl et al, 1997), smooth muscle (Shih et al, 1994) and vascular endothelial cells (Bardin et al, 1996;St Croix et al, 2000;Sers et al, 1994), although its function in these cells is unclear. It has been reported that activation of Mel-CAM leads to tyrosine phosphorylation of p125 FAK and of paxillin, and is associated with p59 fyn (Anfosso et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication

et al. 2001

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Normal human melanocytes are interspersed singly among keratinocytes along the basement membrane of the epidermis, whereas melanoma cells readily adhere to each other during invasion of the dermis or distant organs. The tumorigenic and metastatic phenotype of melanoma cells often correlates with increased expression of cell ± cell and cell-matrix adhesion receptors. Mel-CAM (MCAM, MUC 18, CD146) is a cell ± cell adhesion receptor highly expressed by melanoma cells but not normal melanocytes. We show here that inhibition of Mel-CAM expression in metastatic melanoma cells using genetic suppressor elements of Mel-CAM cDNA leads to inhibition of adhesion between melanoma cells and to downregulation of the tumorigenic phenotype. Growth was not inhibited in genetic suppressor elements-transduced melanoma cells cultured in monolayers but was inhibited when cells were maintained anchorage-independently in soft agar and greatly reduced in immunode®cient mice. A threedimensional epidermal skin equivalent model demonstrated that Mel-CAM allows melanoma cells to separate from the epidermis and invade the basement membrane zone and dermis. However, melanoma cells with little or no Mel-CAM were poorly invasive, possibly due to their loss of gap junctional communication. These results suggest the multifunctional role of a melanomaassociated cell ± cell adhesion receptor in tumor progression. Oncogene (2001) 20, 4676 ± 4684.

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CD146 (MUC18/MCAM): An activation antigen of human T lymphocytes

Cited by 14 publications

References 0 publications

MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies

MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies

Expression and distribution of MUC18 in human uveal melanoma

Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication

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