Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesothelial cell intercellular adhesion molecule-1 (ICAM-1) has recently been shown to play a role in tumour cell adherence to the peritoneum. However, solid tumours poorly express its most ubiquitous ligand, beta2 integrin. The aim of this study was to investigate the role of the beta2 integrin subunit and CD43, a known ligand for ICAM-1, in the development of peritoneal metastases. beta2 Integrin subunit and CD43 expression was assessed on a number of tumour cell lines. Adhesion of SW1222 and PSN-1 cells to human peritoneal mesothelial cells was investigated using a fluorometric assay incorporating an inhibitory antibody to beta2 integrin and CD43. beta2 Integrin expression was not inducible on these tumour cell lines, but Western blotting demonstrated CD43 expression in all the cancer cell lines examined and cell surface expression was confirmed by flow cytometry. The anti-CD43 antibody significantly reduced adhesion of PSN-1 and SW1222 cells to HPMC, however beta2 integrin inhibition did not reduce tumour cell adhesion. CD43 is expressed by a variety of carcinoma cell lines, and plays a role in tumour cell-peritoneal adhesion probably via interactions with its putative ligand ICAM-1.
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PMID:Tumour-expressed CD43 (sialophorin) mediates tumourmesothelial cell adhesion. 1544 12

Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade, and metastasize. Vascular endothelial growth factor (VEGF), a specific mitogen to endothelial cells, is a crucial factor for tumor angiogenesis. In this study, we investigated whether minodronate, a newly developed nitrogen-containing bisphosphonate, could inhibit melanoma growth and improve survival in nude mice by suppressing the VEGF signaling. We found here that minodronate inhibited melanoma growth and improved survival in nude mice by suppressing the tumor-associated angiogenesis and macrophage infiltration. Minodronate completely inhibited the VEGF-induced increase in DNA synthesis and tube formation in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation and Ras activation. Furthermore, minodronate inhibited the VEGF-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in endothelial cells. Minodronate decreased DNA synthesis and increased apoptotic cell death of cultured melanoma cells as well. Our present study suggests that minodronate might suppress melanoma growth and improve survival in nude mice by two independent mechanisms; one is by blocking the VEGF signaling in endothelial cells, and the other is by inducing apoptotic cell death of melanoma. The present study provides a novel potential therapeutic strategy for the treatment of melanoma.
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PMID:Minodronate, a newly developed nitrogen-containing bisphosphonate, suppresses melanoma growth and improves survival in nude mice by blocking vascular endothelial growth factor signaling. 1557 31

Metastasis is a multistep process by which cancer cells, after acquiring several capabilities, spread to distinct sites in the body. It is the major cause of death in individuals suffering from cancer. We have recently identified galectin-7 as a new gene associated with the progression of T cell lymphoma toward a metastatic phenotype, suggesting a possible causal relationship. The present study was designed to investigate the role of galectin-7 in lymphoma. We found that the development of thymic lymphoma was accelerated when induced by lymphoma cells overexpressing galectin-7. Moreover, transfection of an expression vector containing the galectin-7 gene in low metastatic lymphoma cells increased their metastatic behavior and confers these cells with the new ability to overcome the resistance of intercellular adhesion molecule-1-deficient mice to lymphoma dissemination. Finally, we provide data suggesting that galectin-7 modulates the aggressive behavior of lymphoma cells by controlling the expression of metastatic genes, such as MMP-9. This hypothesis is based on the following evidence: (a) galectin-7 transfectants have higher levels of MMP-9 expression, (b) addition of beta-lactose completely inhibits expression of MMP-9 by galectin-7 transfectants, and (c) recombinant forms of galectin-7 induces the expression of MMP-9 in both mouse and human lymphoma cells. Our results have uncovered the existence of a previously undescribed activity, the promotion of cancer cell malignancy, to galectin-7.
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PMID:A novel function for galectin-7: promoting tumorigenesis by up-regulating MMP-9 gene expression. 1595 65

We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression in cancer cells is associated with liver metastasis of colorectal cancer. In this study, we have investigated the effect of ICAM-1 gene transfection into the human colorectal cancer cell line LM-H3 on cell adhesiveness and cytotoxicity of peripheral blood mononuclear cells (PBMC) to cancer cells. Furthermore, we have investigated the effects of this gene transfer on subcutaneous tumour and liver metastases of LM-H3 in nude mice. More PBMC adhered to ICAM-1 transfected LM-H3 cells, LM-H3/ICAM-1, than to non-transfected LM-H3 cells and control LM-H3/Vector. Lysis of LM-H3/ICAM-1 cells by PBMC was significantly increased compared with LM-H3/Vector. Liver metastases with LM-H3/ICAM-1 cells were fewer in number and smaller than metastases with LM-H3/Vector. Intra-tumoural injection of ICAM-1 adenoviral vector significantly inhibited the growth of subcutaneous LM-H3 tumour. In conclusion ICAM-1 gene transfection using adenovirus vector might be an effective therapy for liver metastasis of colorectal carcinoma.
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PMID:Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma. 1605 79

Development of peritoneal metastasis is a significant issue in the treatment of abdominal cancers. Primary interaction between tumour cells and the mesothelium is a vital step in initiating this process. Our aim was to determine the role of the intercellular adhesion molecule-1 (ICAM-1) in mesothelial-tumour adhesion and the effectiveness of therapeutic intervention. Mesothelial cells were derived from omental tissue. ICAM-1 expression in resting state, in the presence of TNF-alpha or after the application of heparin or hyaluronan was determined by flow cytometry. Functional effects on tumour adhesion to a mesothelial monolayer were determined via a Calcein-AM in vitro adhesion assay. In vivo studies were performed utilising 30 WAG/rij rats, which underwent mini-laparotomy with the injection of 1 x 10(5 )CC 513 tumour cells intraperitoneally. Tumour growth was assessed macroscopically and microscopically by two independent examiners. Mesothelial cells expressed high level of ICAM-1, which was up-regulated by the presence of TNF-alpha. The introduction of heparin caused a decrease in ICAM-1 expression, however hyaluronan did not affect the expression. A significant decrease in tumour-mesothelial cell adhesion in vitro and complete aberration of tumour growth in vivo was observed with heparin application. In vitro studies showed utilisation of high molecular weight hyaluronan, which was more limited in vivo. These data imply that heparin may be used as a potential therapeutic through a defined molecular mechanism both in vitro and in vivo. Hyaluronan appears to function as a barrier and hence may be unreliable in blocking peritoneal recurrence.
Clin Exp Metastasis 2005
PMID:ICAM-1 mediated peritoneal carcinomatosis, a target for therapeutic intervention. 1632 Jan 8

MUC1 is a transmembrane glycoprotein expressed by normal breast epithelium and virtually all breast cancers. MUC1 is normally restricted to the apical surface of epithelia and loss of this polarized distribution in breast carcinomas is associated with lymph node metastasis. Our previous work found that MUC1 can bind intercellular adhesion molecule-1 (ICAM-1), mediating adhesion of breast cancer cells to a simulated blood vessel wall, and also triggering a calcium-based signal in the MUC1-bearing cells. It is possible that the depolarized membrane distribution of MUC1 in breast carcinomas may facilitate interactions with stromal/endothelial ICAM-1 leading to adhesion and subsequent migration through the vessel wall. In the current study, we provide evidence that ICAM-1 can influence the migration of cells that express endogenous or transfected MUC1. Migration across a gelatin-coated Transwell membrane could be increased in a step-wise manner by the sequential addition of ICAM-1-expressing cells (endothelial cells and fibroblasts), and ICAM-1-inducing inflammatory cytokines (tumour necrosis factor-alpha and interleukin-1 beta). Antibodies against MUC1 or ICAM-1, but not a control antibody, could abrogate migratory increases. Cells that did not express MUC1 were unresponsive to ICAM-1. Our current findings build on our earlier work, by suggesting that the end result of the MUC1/ICAM-1-mediated cell-cell adhesion and calcium-based signal is migration. This has implications for the exit of circulating tumour cells from the vasculature, as well as tumour cell migration through fibroblast-containing stroma underlying the endothelial wall.
Clin Exp Metastasis 2005
PMID:MUC1 mediates transendothelial migration in vitro by ligating endothelial cell ICAM-1. 1632 Jan 10

Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells to form metastases at distant sites. These processes require alterations in cell-cell and cell-extracellular matrix interactions. As cell adhesion molecules play a role in cell-cell and cell-extracellular matrix adhesion and interactions they are involved in the process of tumour invasion and metastases. In epithelial tissues, receptors of the integrin family mediate adhesion to the adjacent matrix whereas cadherins largely mediate intercellular adhesion. These and other cell adhesion molecules such as intercellular adhesion molecule-1, CD44, dystroglycans and selectins, are involved and undergo changes in carcinomas, which provide possible targets for anti-cancer drug treatments. In the extracellular matrix that is associated with tumours, laminin 5, oncofetal fibronectin and tenascin C appear. The degree of expression of some of these moieties indicates prognosis in oral cancer and offer targets for antibody-directed radiotherapy. Metalloproteases which degrade the extracellular matrix are increased in carcinomas, and their activity is necessary for tumour angiogenesis and consequent invasion and metastases. Metalloprotease inhibitors have begun to produce decreases in mortality in clinical trials. This report provides a brief overview of our current understanding of cell adhesion molecules, the extracellular matrix, tumour invasion and metastasis.
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PMID:Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. 1764 63

Tumor metastasis is a complex process involving the interaction between tumor cells and endothelial cells in which some adhesion molecules play an important role. It was our aim to investigate the role of the adhesion molecules, alpha v beta 3 and alpha v beta 5 and their ligands, developmental endothelial locus-1 (Del-1) and L1, in tumor cell adhesion to endothelial cells in vitro. In this study, the expression and regulation of alpha v beta 3, alpha v beta 5 and intercellular adhesion molecule -1 on liver sinusoidal endothelial cells and liver cancer endothelial cells (T3A) were analyzed by real-time PCR and fluorescent-activated cell sorter. The expression and regulation of the integrin ligands, Del-1 and L1, in six tumor cell lines were analyzed by real-time PCR and western blot. We found the expressions of alpha v beta 3 and alpha v beta 5 were higher on T3A than that on liver sinusoidal endothelial cells, whereas expression of intercellular adhesion molecule-1 was lower on T3A than that on liver sinusoidal endothelial cells. After 24 h hypoxia, the expressions of alpha v beta 3 and alpha v beta 5 were upregulated on T3A and liver sinusoidal endothelial cells; the expression of intercellular adhesion molecule-1 was increased on liver sinusoidal endothelial cells, but remained unchanged on T3A. Del-1 and L1 expression levels were obviously diverse in various tumor cell lines and differentially modulated after 12 h hypoxia. The adhesion of tumor cells with Del-1 and L1 expression was higher in T3A than that in liver sinusoidal endothelial cells, and was significantly increased under hypoxic conditions. Interestingly, the tumor cell adherence could be inhibited by antibodies against alpha v beta 5 and alpha v beta 5, but not by an antibody against intercellular adhesion molecule-1. The adhesion of tumor cells without Del-1 and L1 expression was also higher on T3A than that on liver sinusoidal endothelial cells, but the adhesion could not be inhibited by antibodies against alpha v beta 5, alpha v beta 5 or intercellular adhesion molecule-1, suggesting that other receptors are involved. In conclusion, alpha v beta 5, alpha v beta 5 and their ligands Del-1 and L1 play an important role in the process of tumor cells moving from the original place.
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PMID:The role of adhesion molecules, alpha v beta 3, alpha v beta 5 and their ligands in the tumor cell and endothelial cell adhesion. 1809 Jan 24

Breast cancer is the most commonly diagnosed malignancy in women worldwide. Metastatic development is associated with poor prognosis and current therapies provide only limited success. Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a wild-type common-cold producing enterovirus, is an effective oncolytic agent against human melanoma xenografts in vivo. CVA21 specifically targets and lytically infects susceptible cells expressing the CVA21 cellular receptors, intercellular adhesion molecule-1 (ICAM-1) and/or decay-accelerating factor (DAF). Herein, the efficacy of CVA21 as a therapeutic agent against human breast cancer was investigated both in vitro and in vivo. Flow cytometric analysis revealed that the human breast cancer cell lines examined expressed significantly elevated levels of surface ICAM-1 and DAF compared to normal breast cell lines, and that all cancerous lines were more susceptible to lytic infection by CVA21 than the normal cells. Through the use of subcutaneous (T47D cells) and orthotopic (MDA-MB-231-luc cells) xenograft SCID mouse models it was demonstrated that a single intravenous injection of CVA21 produced significant regression of pre-established tumors in vivo, as well as targeting and elimination of metastases in the orthotopic model. Taken together, these findings highlight the exciting potential of CVA21 as a therapeutic agent against both primary and metastatic human breast cancer.
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PMID:Systemic targeting of metastatic human breast tumor xenografts by Coxsackievirus A21. 1825 29

MUC1, a transmembrane glycoprotein of the mucin family, when aberrantly expressed on breast cancer cells is correlated with increased lymph node metastases. We have previously shown that MUC1 binds intercellular adhesion molecule-1 (ICAM-1) on surrounding accessory cells and facilitates transendothelial migration of MUC1-bearing cells. Nevertheless, the underlying molecular mechanism is still obscure. In the present study, we used a novel assay of actin cytoskeletal reorganization to show that by ligating ICAM-1, MUC1 triggers Rac1- and Cdc42-dependent actin cytoskeletal protrusive activity preferentially at the heterotypic cell-cell contact sites. Further, we show that these MUC1/ICAM-1 interaction-initiated lamellipodial and filopodial protrusions require Src family kinase and CT10 regulator of kinase like (CrkL) accompanied by the rapid formation of a Src-CrkL signaling complex at the MUC1 cytoplasmic domain. Through inhibition of Src kinase activity, we further revealed that Src is required for recruiting CrkL to the MUC1 cytoplasmic domain as well as mediating the observed actin cytoskeleton dynamics. These findings suggest a novel MUC1-Src-CrkL-Rac1/Cdc42 signaling cascade following ICAM-1 ligation, through which MUC1 regulates cytoskeletal reorganization and directed cell motility during cell migration.
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PMID:MUC1 initiates Src-CrkL-Rac1/Cdc42-mediated actin cytoskeletal protrusive motility after ligating intercellular adhesion molecule-1. 1840 35


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