Cellular expression of lymphocyte function associated antigens and the intercellular adhesion molecule-1 in normal tissue.

Smith, Mark E.; Thomas, Jordan

doi:10.1136/jcp.43.11.893

Cited by 100 publications

(41 citation statements)

References 21 publications

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“…Immunohistochemical studies have shown that the distribution of CD54 on normal human tissues is restricted. 40 In vivo administration of another anti-CD54 antibody into cynomologous monkeys prolonged renal allograft survival without damaging normal tissues. 41 Moreover, clinical trials in patients treated with another anti-CD54 antibody for the prevention of kidney allograft rejection 42 or the treatment of rheumatoid arthritis 43 have demonstrated that anti-CD54 is safe and has no overt toxicity.…”

Section: Discussionmentioning

confidence: 99%

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Wang

Coleman

Pop

et al. 2005

Intl Journal of Cancer

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We have shown that administration of a novel anti-CD54 monoclonal antibody (UV3) results in long-term survival of SCID mice bearing human myeloma xenografts. Previous studies have demonstrated a link between the expression of CD54 and the progression of uveal melanoma. Our study assessed the expression of CD54 on 7 human uveal melanoma cell lines and 3 cell lines established from uveal melanoma metastases. In vivo studies examined the efficacy of systemic and local administration of UV3 antibody on the progression of uveal melanoma cells transplanted either heterotopically or orthotopically into SCID mice. Five of the 7 primary uveal melanoma cell lines and all 3 of the metastases cell lines expressed CD54. Intraperitoneal injection of either IgG or F(ab 0 ) 2 fragments of UV3 significantly inhibited the growth of subcutaneous and intraocular melanomas. Subconjunctival injection of either IgG or F(ab 0 ) 2 fragments of UV3 produced a significant reduction in the growth of intraocular melanomas, even if the antibody was administered after the appearance of intraocular tumors. The results indicate that both primary and metastatic human uveal melanoma cells express CD54. The marked inhibition of intraocular and subcutaneous uveal melanoma progression suggests that UV3 antibody is a promising therapeutic agent for further evaluation in patients with uveal melanoma. This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma. ' 2005 Wiley-Liss, Inc.Key words: anterior chamber; eye; CD54; immunotherapy; uveal melanoma Uveal melanoma is the most common intraocular malignancy in adults and occurs with a frequency of 6 to 7 cases per one million adults. 1 Although cutaneous and uveal melanomas share a neural crest origin, they differ significantly in their epidemiological, 2 cytogenetic 3 , metastatic 4-6 and immunological 4 characteristics. One of the remarkable differences between cutaneous and uveal melanomas is their metastatic behavior. Although skin melanomas metastasize to almost any organ, uveal melanoma displays a propensity to spread to the liver. Indeed, liver metastases are present in up to 95% of the patients who die from uveal melanomas. [7][8][9][10] Although there have been advances in the treatment of primary uveal melanomas, the 5-year survival rate for uveal melanoma patients has not improved in the past 30 years. 1,10 Moreover, no therapeutic modality prevents the metastasis of uveal melanoma or prolongs the survival of patients. 11 Studies have suggested a correlation between the expression of CD54 and the progression of skin and uveal melanomas. 12,13 Expression of CD54 was detected in 81-85% of human uveal melanoma specimens. 13,14 Reduced expression of CD54 in primary uveal melanomas has been associated with increased metastatic disease. 13 CD54 is an important ligand for leukocytes and is believed to be involved in immune surveillance. 15,16 Intravenous administration of MAb against human CD54 (U...

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Section: Discussionmentioning

confidence: 99%

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Wang

Coleman

Pop

et al. 2005

Intl Journal of Cancer

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“…VCAM-1, whilst largely present on activated endothelial cells, is also present on dendritic cells, neuronal cells and renal parietal epithelium (Rice et al, 1991), and in lymphoid malignancies shows a similar pattern of expression to that of E-selectin (Ruco et al, 1992). ICAM-1, which is elevated to a greater extent and in a greater proportion of these cancer patients, has a much wider cellular distribution (Smith & Thomas, 1990) and in addition to endothelial cells has been described on normal and malignant epithelial tissue including melanoma cell lines and primary tissue, renal cell lines and intestinal cell lines (Natali et al, 1990;Tomita et al, 1990;Becker et al, 1991). Thus at least some of the soluble ICAM-1 present in sera of cancer patients is probably derived from tumour tissue.…”

Section: Sera and Patientsmentioning

confidence: 99%

“…ICAM-1, the inducible ligand for lymphocyte function associated antigen-I (LFA-1) and Mac-i, is found on endothelial cells, leukocytes and some epithelial tissue (Smith & Thomas, 1990), and plays a major role in cell-cell interactions in inflammatory and immune responses. It has also been implicated in the progression of melanoma (Natali et al, 1990).…”

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confidence: 99%

Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies

Banks

Gearing²,

Hemingway³

et al. 1993

Br J Cancer

287

153

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Summary Cellular adhesion molecules have been implicated in tumour progression and metastasis. This study examines for the first time the serum concentrations of circulating VCAM-1 and E-selectin in a consecutive series of 110 cancer patients seen in a general medical oncology clinic, and confirms and extends previous studies reporting measurement of circulating ICAM-1. Soluble ICAM-1 and VCAM-1 levels were significantly higher in all the patient groups compared with the controls whereas soluble E-selectin was significantly higher in the ovarian, breast and GI cancer groups and lower in the myeloma group. The significance of these results together with the possible sources and stimuli for release of these adhesion molecules are discussed. Sera and patientsBlood samples were obtained from a consecutive series of all patients being seen in a general medical oncology clinic, including those with both localised or advanced disease and those on active therapy or during follow-up. The following malignancies were represented: bladder (n = 6), breast (n = 13), gastrointestinal (n = 18), ovarian (n = 15), renal (n = 12), Hodgkin's disease (n = 15), non-Hodgkin's lymphoma (n = 13), and myeloma (n = 18). Approximately 85% of those with epithelial cancers had clinical evidence of metastases. Samples were allowed to clot, and the serum stored at -70'C until assayed. Samples were also obtained from 89 healthy laboratory and clinical personnel and blood donors (age range 18-60 years) and assayed for E-selectin and VCAM-1. In the case of ICAM-1, a sub-group of 27 of the control samples (age range 24-54 years) were assayed.Assay of soluble adhesion molecules Levels of circulating ICAM-1 were measured with a commercial ELISA kit (British Bio-technology Products, Oxford, UK). Concentrations of circulating E-selectin and VCAM-1 were measured using dual monoclonal antibody two-site ELISAs Pigott et al., 1992). Briefly, microtitre ELISA plates (Nunc Immunoplates, Life Technologies, Paisley, Scotland) were coated overnight with a specific capture antibody (BBIG-E2 for E-selectin, BBIG-V4 for VCAM-1) at a final concentration of 10 tg ml-' in 0.1 M bicarbonate buffer pH 8.9. Standards and samples were added to the plate, incubated for 2 h at room temperature and the bound soluble adhesin of interest was detected by sequential incubation with a specific biotin-labelled antibody (BBIG-E5 for E-selectin, BBIG-V3 for VCAM-1) followed by horseradish peroxidase-conjugated streptavidin (Amersham International, Amersham, UK) and finally tetramethylbenzidine (Universal Biologicals, Kingston-upon-Thames, UK). The reaction was stopped by the addition of 1 M HCI to each well and the O.D. 450 nm measured using a Titertek MS-2 reader (ICN Flow, Rickmansworth, UK). The assays were standardised using a recombinant soluble form of Eselectin or VCAM-1 (Pigott et al., 1991) lacking their transmembrane and cytoplasmic domains and given an arbitrary unitage against which all samples were measured.Statistical analysis Data was analysed using SPSS/PC + . Res...

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“…Cytocentrifuge preparations of cell lines were air-dried (30 to 60 rain; 22 °C) fixed in cold (4 °C) acetone for 5 rain and examined immunocytochemically by the peroxidase-anti-peroxidase (PAP) method (Smith & Thomas, 1990). MAbs were used to define the following cellular antigens: vimentin (V9, Dako); CD23 (MHM6 from A. McMichael, University of Oxford, U.K.); CD21 (HB5, Becton Dickinson); CD30 (BerH2, Dako); CD39 (AC2, Serotec); C D l l a [leukocyte function antigen (LFA)-I, MHM24 from A. McMichael]; CD54 (intercellular adhesion molecule (ICAM)-I; RRI/1) and CD58 (LFA-3, TS2/9) (both from T. Springer, Harvard Medical School, U.S.A.); CD77 (BL antigen from J. Wiels, Institut Gustav Roussy, France); and CD10 (J5, Orthomune).…”

Section: E T H O D Smentioning

confidence: 99%

Epstein--Barr virus (EBV) nuclear antigen 6 induces expression of the EBV latent membrane protein and an activated phenotype in Raji cells

Allday

Crawford

Thomas

1993

Journal of General Virology

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Epstein-Barr virus (EBV) nuclear antigen (EBNA) 6 (also known as 3c) is a latent nuclear protein with an Mr of about 160K which is invariably expressed in EBVimmortalized B cells. It includes a putative basic leucine zipper domain; as such it is a good candidate for a regulator of viral gene expression. More than 75 % of the EBNA 6 coding sequence is deleted from viral genomes carried in the Burkitt's lymphoma (BL) tumour-derived cell line, Raji. Thus although Raji cells express normal levels of the remaining five EBNAs and low levels of latent membrane protein (LMP), EBNA 6 protein is completely absent. In this study we have established Raji clones stably expressing EBNA 6 after cotransfection of an EBNA 6 gene under the control of the simian virus 40 early promoter with a selectable marker. Analysis of these clones has revealed that EBNA 6 induces a significant increase in the expression of LMP. In addition the cells have undergone a number of morphological and phenotypic changes consistent with blastactivation of normal B lymphocytes. The Raji cells expressing EBNA 6 show ruffling of the cell membrane and the development of a polarity defined by multiple villous (' spiky') projections at one end of the cell. This morphological change is associated with a dramatic increase in the expression of the cytoskeletal protein, vimentin. The EBV-associated B cell activation marker CD23 (blast 2) is induced to high levels although other activation markers such as CD30 and CD39 are unaffected. All these changes appear to be independent of the precise levels of EBNA 6 protein expressed. EBNA 2 has been shown previously to trans-activate the LMP gene and in the control Raji cells, EBNA 6-positive Raji cells and in B lymphoblastoid cells similar levels of EBNA 2 are expressed. Our findings are therefore most consistent with a model in which EBNA 6 either augments or complements the action of EBNA 2 in the induction of LMP and the cascade of gene expression which leads to B cell activation and immortalization by EBV.

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Cellular expression of lymphocyte function associated antigens and the intercellular adhesion molecule-1 in normal tissue.

Cited by 100 publications

References 21 publications

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies

Epstein--Barr virus (EBV) nuclear antigen 6 induces expression of the EBV latent membrane protein and an activated phenotype in Raji cells

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