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)

Human endothelial cells were transiently transfected with E-Selectin which enabled us to study tumor cell/endothelial interactions following engagement of E-Selectin without the added complications of metabolic stimulation, morphological changes, and/or up regulation of other adhesion molecules due to cytokine induction. Similar results were received from in vitro binding studies and FACS analyses on both Tumor Necrosis Factor-alpha activated and E-Selectin transfected endothelial cells. These data suggest that this methodology is appropriate for dissecting the individual activities of E-selectin while minimizing the participation of other adhesion molecules, thereby allowing us to develop a better understanding of the role of E-Selectin and endothelia in metastatic disease.
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PMID:Cancer cell binding to E-selectin transfected human endothelia. 128 Apr 20

The interaction of tumor cells with endothelial cells is a key event in tumor metastasis. We established an in vitro invasion assay system, in which the invasion of tumor cells after interaction with endothelial cells can be examined. Two chamber culture wells separated by porous membrane were used. Human umbilical vein endothelial cells (HUVEC) were placed on porous membranes coated with matrix components. The invasion by HT1080 fibrosarcoma cells was determined in this system by counting the number of cells that moved through the membranes from upper to lower chambers. HUVEC cells did not migrate through the membranes as judged by the staining with UEA-I. Observation by scanning electron microscopy revealed that HT1080 cells bound to HUVEC surfaces and migrated underneath the HUVEC monolayer. Effects of antibodies specific for cell surface adhesion molecules on the migration of HT1080 cells were examined. Invasion of uncoated membranes and membranes coated with HUVEC cells was compared. Antibody against E-selectin significantly suppressed an increase of HT1080 cell invasion of HUVEC monolayers stimulated by IL-1 beta or TNF alpha. Antibody against integrin alpha 3 subunit remarkably inhibited the invasion of HUVEC cell-coated membranes, suggesting that integrins with the alpha 3 subunit may play an important role in the transendothelial invasion by HT1080 cells.
Clin Exp Metastasis 1994 Jul
PMID:A novel in vitro assay system for transendothelial tumor cell invasion: significance of E-selectin and alpha 3 integrin in the transendothelial invasion by HT1080 fibrosarcoma cells. 751 60

We investigated the interaction between pancreas carcinoma and endothelium, using the originally established human pancreas carcinoma cell lines (PCI), and reported the importance of E-selectin and sialyl Lewis(a) in the adhesion of pancreas carcinoma cells to endothelium activated by inflammatory cytokines. Interestingly, the attachment of PCI to endothelial cells was augmented by preincubation of PCI with endothelial cells through an upregulated E-selectin expression on endothelial cells. Major factor of this activity was IL-1 alpha which was produced by pancreas carcinoma cells. We supposed that tumor-derived IL-1 alpha may contribute to the hematogenous metastasis of cancers in non-inflamed, distant location. In addition to IL-1 alpha, IL-6 also was produced by some, but not all, of PCI cell lines. An endothelial permeability was increased only when endothelial cells were pretreated with the culture supernatant of IL-6-producing cell lines. The activity of supernatant was inhibited by specific antibody reactive for IL-6. Using a liver metastatic model in the nude mouse, we investigated the importance of sialyl Lewis(a) expression and IL-6 production by pancreas carcinoma for progression of metastasis in vivo. Sialyl Lewis(a)-positive cell lines generated more numerous metastatic colonies in the liver than sialyl Lewis(a)-negative cell lines did. PCI lines that produce IL-6 generated significantly less metastases in both number of liver nodules and incidence itself than IL-6-producing PCI did, therefore, surface expression of sialyl Lewis(a) and production of IL-6 appear to be important modulators that regulate hematogenous metastasis of pancreas carcinoma.
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PMID:[Mechanism of blood-borne metastasis in relation to the interaction between pancreatic carcinoma and endothelial cells]. 763 17

The cutaneous lymphocyte-associated antigen (CLA) is the T-cell ligand for E-selectin and is involved in tissue selective migration of memory/effector T cells to chronic inflammatory sites in skin. Here, we examine the hypothesis that CLA is also involved in the local host immune response to cutaneous neoplasms. Eleven primary cutaneous melanomas, nine primary cutaneous squamous cell carcinomas, and 11 assorted neoplasms metastatic to cutaneous and noncutaneous sites were immunostained with anti-CLA (HECA-452), as well as antibodies directed against B cells (CD20), T/NK cells (CD43), and memory/effector T cells (CD45RO). Essentially all of the lymphocytes surrounding and infiltrating both the cutaneous and noncutaneous tumors were CD43+/CD20-, and most expressed the memory/effector marker CD45RO. CLA was expressed on 10 to 80% (mean: 50%) of T cells associated with primary cutaneous neoplasms (including both melanomas and squamous cell carcinomas) but was essentially absent from noncutaneous primaries (including those metastatic to dermis) and from cutaneous primaries metastatic to dermis or other sites. Overall, the results suggest that CLA+memory T cells are a major component of the local host immune response to cutaneous neoplasms and are likely recruited to the skin by site-specific rather than tumor-specific mechanisms. The lack of a CLA+T-cell response to dermal metastases suggests that epidermal involvement may be required to attract this subset.
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PMID:Lymphocytes infiltrating primary cutaneous neoplasms selectively express the cutaneous lymphocyte-associated antigen (CLA). 768 98

Human colorectal carcinomas with increased metastatic potential and with poor prognosis are characterized by the high content of sialyl-LeX carbohydrate antigens. The levels of these carbohydrate antigens apparently increase during colorectal carcinoma progression from non-metastatic to metastatic tumors. The levels of tumor-associated sialyl-LeX antigens are inversely correlated to the post surgical survival of colon carcinoma patients as revealed by retrospective studies. Cell lines selected for high levels of cell surface sialyl-LeX antigens metastasize to livers when they are injected intrasplenically into nude mice. The highly expressing cells also strongly adhere to activated endothelial cells apparently through E-selectin. We conclude that sialyl-LeX carbohydrate antigen is a unique molecular phenotype that determines colorectal cancer metastasis.
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PMID:Colorectal cancer metastasis determined by carbohydrate-mediated cell adhesion: role of sialyl-LeX antigens. 790 54

This study examined the ability of the recombinant human interleukin 1 receptor antagonist (IL-1ra) to block interleukin 1 (IL-1)-mediated experimental metastases from the A375M human melanoma. In vivo, IL-1ra administrated at concentrations > or = 200 times IL-1 significantly inhibited the increase in lung colonies induced by IL-1 in nude mice. The response to IL-1 was significantly inhibited when IL-1ra was administered simultaneously with or 1 to 3 h before IL-1. In vitro, the incubation of IL-1-activated endothelial cells with IL-1ra prevented the increase in adhesion of A375M melanoma cells. At the same experimental conditions, IL-1ra inhibited the augmented expression of the intracellular and vascular cell adhesion molecules 1 and E-selectin induced by IL-1 on endothelial cells. Lipopolysaccharide, an IL-1 inducer, increased the number of lung colonies in nude mice. IL-1ra injected with or 1 h after lipopolysaccharide inhibited this augmentation, suggesting a role for host-produced IL-1 in metastasis formation.
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PMID:Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system. 826 95

Prostacyclins have long been shown to have anti-metastatic activity. One hypothesis is their modulation of cell adhesion molecule (CAM) expression by target organ endothelial cells. We have postulated that prostacyclin, its analogs, and mechanistic mimics decrease colon carcinoma adhesion to cytokine-stimulated endothelial cells by blocking endothelial expression of the adhesion molecule E-selectin, but not the vascular cell adhesion molecule-1 (VCAM-1). Cultured human microvascular endothelial cells (HDMEC) were pre-incubated with prostacyclin (PGI2), dibutyrl-cAMP (dbcAMP), forskolin (FOR), and/or iso-methylbutylxanthine (IBMX) for 15 min, then co-incubated with the cytokine tumor necrosis factor (TNF) for 4 h. HDMEC surface expression of E-selectin and VCAM-1 was evaluated by flow cytometry and ELISA. Adherence of 51Cr-labeled colon carcinoma cells to HDMEC monolayers was then determined. In parallel assays, HDMECs were incubated with anti-E-selectin and anti-VCAM-1 monoclonal antibody (1:100) prior to the addition of tumor cells. Prostacyclins, its analogs, and mimics significantly reduced E-selectin expression by HDMEC, while the reduction of VCAM-1 expression was much less pronounced. Prostacyclins also significantly decreased colon carcinoma adherence to stimulated HDMECs. The inhibition of E-selectin expression, but not VCAM-1 expression, corresponded to the reduction of tumor cell adherence. Prostacyclin's effects on tumor adhesion were nullified by pre-incubation with E-selectin antibody. The inhibition of colon carcinoma adherence to cytokine-stimulated endothelial cells treated with prostacyclin, its analogs, and mimics appears to result from blocking endothelial E-selectin, but not VCAM-1, expression. These data support the hypothesis that prostacyclins may exert their anti-metastatic effect, in part, by inhibiting CAM-mediated adherence of colon carcinoma to endothelial cells in metastatic target organs.
Clin Exp Metastasis 1996 May
PMID:Anti-metastatic prostacyclins inhibit the adhesion of colon carcinoma to endothelial cells by blocking E-selectin expression. 867 77

E-selectin, an endothelial cell adhesion molecule, mediates the initial step of leucocyte adhesion to activated vascular endothelium. The soluble isoform of E-selectin promotes angiogenesis in rat cornea. In the present study, we investigated whether leucocyte adhesion and angiogenesis are also involved in tumour progression and metastasis of colorectal cancer. Therefore, we determined the level of circulating soluble E-selectin in serum samples of 38 patients with colorectal cancer; 20 patients with non-metastatic and 18 patients with metastatic disease. Median levels of soluble E-selectin were found to be significantly higher in metastatic tumour disease (88.7 ng/ml, range 25-203 ng/ml) than in healthy controls (34.9 ng/ml, range 15-59 ng/ml, P = 0.01), in patients with primary tumours or with local recurrences (39.5 ng/ml, range 22-100 ng/ml). Furthermore, there was no correlation with the serum level of C-reactive protein, fibrinogen or tumour necrosis factor alpha suggesting that the elevation of E-selectin is independent of inflammation in tumour patients. Therefore, we propose that elevated soluble E-selectin may reflect increased neovascularisation in metastatic tumour tissue.
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PMID:Elevated serum E-selectin in patients with liver metastases of colorectal cancer. 875 56

Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GMI-treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI-10, -19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis(a) (SLe(a)), VLA-4/6, LFA-I/3, CEA, E-selectin, VCAM-I, NCAM, Mac-I, HLA-ABC/ DR/DQ, ICAM-I/2, production of interleukin-I alpha, tumor necrosis factor-alpha, and matrix metalloproteinase, as well as susceptibility to cytotoxicity by natural killer cells, were all examined. Expression of surface SLea was significantly associated with metastasis; numbers of metastatic colonies of SLe(a)-positive and -negative cell lines were 21.6 +/- 33.9 and 6.5 +/- 14.3 (p < 0.01), respectively. Moreover, the intensity of surface SLe(a) expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe(a) monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM-I expression and liver metastasis was noted, the species-restricted function of ICAM-I makes interpretation difficult. Collective evidence indicates that expression of SLe(a) is an important positive mediator in the hematogenous metastasis of pancreas carcinoma.
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PMID:Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: the importance of surface sialyl Lewis(a) antigen. 879 70

E-selectin which is expressed on endothelial cells plays an important role in the adhesion of cancer cells to the vascular endothelium, being the ligand for a carbohydrate antigen expressed on cancer cells. In this study, the clinical usefulness of this protein was examined. E-selectin was expressed on the endothelial cells of the small vessels adjacent to the cancer nests in 63 of the 104 (60.6%) primary tumors of breast cancer. The expression of E-selectin in locations adjacent to the cancer nests was more pronounced than that in distant ones. The mean value of serum soluble E-selectin (ng/ml) was 38.3 in benign breast disease, 47.8 in those with no evidence of recurrence, 49.4 in stage I/II primary breast cancer, 75.8 in stage III/IV primary breast cancer, and 93.7 in recurrent breast cancer. The mean value of serum soluble E-selectin was 106.2 ng/ml in patients with distant metastases, and 50.4 ng/ml in those with no evidence of distant metastases. Thus, the concentration of soluble E-selectin was significantly elevated in the sera of patients with distant metastases. These findings suggested that cancer cells induced the expression of E-selectin on endothelial cells and, that serum soluble E-selectin is useful as a tumor marker having a close relationship to metastasis in breast cancer.
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PMID:Increased concentration of soluble E-selectin in the sera of breast cancer patients. 913


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