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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcomas and rhabdomyosarcomas are vigorously invading tumors. Before they can extravasate to the parenchymal organs and form metastases, they have to adhere to the endothelial cells lining the blood vessels and then penetrate through the endothelium. We show that several human sarcoma cell lines, osteosarcomas HOS, MG-63, U2-OS, and a rhabdomyosarcoma RD, express VLA-4 molecule on their surface and bind to the VCAM-I-expressing activated endothelial cell line Ea.hy 926. The increased sarcoma-cell adhesion could be abolished by treating the sarcoma cells with monoclonal antibodies (MAbs) VLA4 (both alpha- and beta-chain, HP2/1 and 4B4 respectively) or treating endothelial cells with VCAM-I antibody (4B9). Furthermore, we show that sarcoma cells adhere to recombinant soluble VCAM-I protein. On the other hand, these sarcoma cell lines do not express marked amounts of other ligands (such as CDII/18 or sialyl-Lex) for other endothelial adhesion molecules (ICAM-I, ICAM-2, E- and P-selectin) indicating that the VLA-4-VCAM-I dependent pathway might be of major importance in sarcoma extravasation. VLA-4 is not always in an avid form and therefore the expression of VLA-4 does not directly predict adherence to VCAM-I. The avidity of VLA-4 (measured by adherence to soluble VCAM-I) of MG-63 and U2-OS cells could be increased by a 30-min PMA treatment, whereas the avidity of VLA-4 on HOS cells increased only after 48 hr of PMA induction. Our results show that sarcoma cell lines (HOS, MG-63, U2-OS and RD) adhere to stimulated endothelium via VLA-4-VCAM-I adhesion molecules and that VLA-4 avidity on sarcoma cells can be differentially modulated by PMA.
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PMID:VLA-4 integrin on sarcoma cell lines recognizes endothelial VCAM-1. Differential regulation of the VLA-4 avidity on various sarcoma cell lines. 128 Nov 43

Human neural-crest-derived tumor cell lines, including three neuroblastomas, an astrocytoma, a glioblastoma, a rhabdomyosarcoma and a melanoma were screened for the expression of the integrin alpha 4 beta 1 (VLA-4). The neuroblastomas IMR-32 and SK-N-SH, the astrocytoma 131-INI, the glioblastoma Fogerty and the rhabdomyosarcoma TE-671 expressed alpha 4 beta 1 as determined by cytofluorometry and immunoprecipitation. Another neuroblastoma line, LA-N-1, did not express alpha 4 beta 1. Analysis of immunoprecipitated alpha 4 beta 1 showed that the alpha 4 subunit from the various cell types differed in relative molecular weight (M(r)). The variability in the observed M(r) could be accounted for by differences in the levels of N-linked glycosylation. The observed variability in M(r) did not appear to affect function since intact cells and solubilized alpha 4 beta 1 bound to a synthetic peptide identical in sequence to the CS-1 region of the alternatively spliced IIICS domain of fibronectin, a known alpha 4 beta 1 ligand.
Clin Exp Metastasis 1992 Jul
PMID:Expression and ligand-binding function of the integrin alpha 4 beta 1 (VLA-4) on neural-crest-derived tumor cell lines. 153 75

Recently, many surface proteins of lymphoid cells that mediate adhesion to other cells and extracellular matrix have been identified. Several of these cellular adhesion molecules (CAM) are also expressed by metastatic lymphoma cells and may mediate adhesion to tissue components during the metastatic process. Correlations observed between expression of certain CAM, like MEL-14 and CD44, and particular patterns of spread, support this notion, but conclusive evidence is scarce. We have used T-cell hybridomas to study the mechanisms of wide-spread lymphoid metastasis. The results obtained with this model are reviewed here. The advantages are that a large number of genetically similar cell lines can be generated, which can be grouped in large panels of highly invasive and non-invasive cells. Invasiveness of these cells in hepatocyte and fibroblast monolayers correlates with experimental metastasis. Lymphoid CAM that are potentially involved in metastasis are reviewed. Several of these CAM are not, or not consistently, expressed by the invasive T-cell hybridomas, indicating that they are not indispensable. Notably, some of the CAM involved in the onset of an immune response or in migration into inflamed tissues, like ICAM-1 and VLA-4, and the 'homing receptors' MEL-14 and LPAM-1 do not seem to be involved. CAM that are consistently expressed by the T-cell hybrids include LFA-1, the beta-1 integrin subunit CD29, CD31 (PECAM-1) and CD44 ('Hermes homing receptor'). We have generated considerable evidence that LFA-1 is required for efficient metastasis of T-cell hybrids, based on the behavior of LFA-1-deficient mutants and revertants. High levels of LFA-1 are required. The relevant counterstructure is probably ICAM-2 rather than ICAM-1. Preliminary results suggest that also a beta-1 integrin, possibly VLA-5, plays a role. Finally, we summarize evidence indicating that CD31 and CD44 are primary candidates for involvement in metastatic spread of T-cell hybridomas.
Cancer Metastasis Rev 1991 May
PMID:Adhesion molecules in lymphoma metastasis. 168 May 76

Many steps in melanoma metastasis involve cell-cell or cell-matrix adhesive interactions. The surface molecules which mediate these processes therefore play an important role in regulating melanoma dissemination and their level of expression may alter during the course of tumor progression. Human melanocyte strains and melanoma cell lines have been characterised with regard to levels of cell surface receptors of the integrin family. Increased amounts of at least two integrins, VLA-4 (alpha 4 beta 1) and VnR (alpha v beta 3), appeared to correlate with progression in this tumor, type. A novel VnR composed of an alpha v beta 1 association has been observed in one melanoma cell line and there is the possibility that heterogeneity of integrin composition could affect biological behavior of these tumors. CD44, a cell surface glycoprotein which functions as the major receptor for hyaluronate, is another molecule whose expression increases in transformed cells of the melanocytic lineage. Iterative sorting on the FACS for stable variants, of both human and murine melanomas, expressing low and high levels of CD44 established that lack of expression of this molecule correlated with impaired ability to form pulmonary tumor nodules subsequent to i.v. injection into appropriate recipient mice. These findings illustrate that an understanding of the regulation of melanoma adhesion receptors could provide insights into the process of tumor spread.
Cancer Metastasis Rev 1991 Jun
PMID:Cell adhesion receptor expression during melanoma progression and metastasis. 187 52

This investigation has focused on whether a number of molecular species, which have recently been recognised as components of cell attachment receptors utilised in recirculatory leukocyte traffic, are expressed on metastatic tumour cell populations. This has been studied on live cultured metastatic and non-metastatic tumour cell lines as well as on histological sections of frozen tissue from primary tumours and metastases which they formed after inoculation into nude mice. Here we report data we have obtained using immunofluorescence microscopy, fluorescence activated cell analysis, immunocytochemistry and pathological investigation of tumour behaviour in vivo, which converge to indicate that expression of the integrin molecule VLA-4 is positively associated with the execution of the metastatic process. This molecule is known to be a receptor for at least two ligands, namely the inducible endothelial adhesion molecule VCAM-1 and the extracellular matrix component fibronectin, and is thought to be mechanistically important in the attachment and diapodesis of lymphocytes. The present findings, indicating differential expression of this molecule on metastatic cell populations relative to non-metastatic cell populations, support and extend recent reports from other laboratories, of the presence of various leukocyte adhesion receptors on metastatic tumour cells. This accumulating evidence suggests that inappropriate expression of one or more of these surface adhesion molecules in tumour cell lineages may endow the progeny of the affected clones with some of the properties needed for metastatic behaviour. The total information so far assembled by various groups also provides some early clues suggesting that the types of molecules expressed may be related to the histogenetic origin of the tumour and its pattern of metastatic spread.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of VLA-4 integrin expression with metastatic potential in various human tumour cell lines. 768 91

A static adhesion assay employing 6-carboxy-3',6'-diacetylfluorescein (6-CFDA) as a fluorescent marker has been developed to study the interactions of tumour cell lines with endothelial monolayers. This assay allows simple, safe quantification of cell-cell adhesion using living cells. It has been used to demonstrate that the integrin adhesion molecule VLA-4 mediates the attachment of RPMI-7951 melanoma cells to human umbilical vein endothelial cells (HUVEC) which have been activated by TNF alpha. In addition, MDA-MB-231 breast adenocarcinoma cells display greater adhesion to microvessel endothelial cells than to large vessel endothelial cells.
Clin Exp Metastasis 1995 May
PMID:A simple fluorometric assay for quantifying the adhesion of tumour cells to endothelial monolayers. 775 Feb 3

Models for experimental metastasis were established to investigate the influence of rmTNF on tumor-colony formation in the liver. Highly metastatic lymphoma tumor cells were either injected i.v. or inoculated s.c. to form spontaneous metastases. In both systems, administration of rmTNF to the animals led to significant enhancement of the number of liver metastases in comparison with control groups. The number of metastatic tumor-cell colonies at an early stage of metastasis was increased, as well as the number of surface metastases in a late stage. Consequently, TNF-treated animals revealed a higher mortality. The optimal time for TNF to exert this metastasis-enhancing effect was found to be 7 days after tumor inoculation. In vitro adhesion of the lymphoma tumor cells to a mouse endothelioma cell line was strongly inhibited by monoclonal antibodies interfering with the interaction of VCAM-1 with VLA-4. These results support and extend earlier results with a fibrosarcoma lung colonization model. In addition, they show that stimulation of the immune system in tumor-bearing hosts activates tumor-promoting pathways, in addition to having possible beneficial effects.
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PMID:Promotion of experimental liver metastasis by tumor necrosis factor. 789 59

We previously reported that a derivative of the interleukin-6 (IL-6)-dependent B9 B-cell hybridoma (B9/LPNU1L) constitutively expressing an interleukin-1 alpha (IL-1 alpha) gene introduced by retrovirus-mediated gene transfer preferentially metastasized to bone marrow following intravenous injection into unirradiated syngeneic BALB/c mice. B9/LPNU1L cells recovered from the femoral marrow of a recipient with hind limb paralysis (denoted B9/BM1) retained their IL-6-dependency yet displayed enhanced metastatic capacity during serial transplantation in vivo. In contrast, autonomously-growing B9 variants spontaneously arising in vitro or IL-6-independent B9 derivatives created by infection with recombinant IL-6 retroviruses rarely gave rise to experimental metastases in syngeneic BALB/c or nude mice. Examination of cell adhesion molecule profiles by immunofluorescence flow cytometry has revealed high levels of CD44, moderate levels of VLA-4 and low levels of LFA-1 on all B9-series cells. By comparison, ICAM-1 expression was significantly elevated on B9/BM1 cells, with independent isolates stably expressing about 4-fold higher levels which were paralleled by corresponding increases in the steady-state levels of ICAM-1 mRNA. L-Selectin was not expressed by any of the cell lines. Despite higher ICAM-1 levels, cell aggregation assays revealed that LFA-1-ICAM-1 adhesive interactions were not involved in the homotypic adhesion of B9/BM1 cells but rather that binding of CD44 to endogenously-synthesized hyaluronan was responsible. Furthermore, B9/BM1 cells expressing high levels of ICAM-1 were found to be less susceptible to cytolysis by natural killer (NK) cells than their weakly metastatic or nonmetastatic counterparts.
Clin Exp Metastasis 1993 Mar
PMID:Association between ICAM-1 expression and metastatic capacity of murine B-cell hybridomas. 809 98

In order to evaluate the significance of adhesion molecules expressed on melanocytic tumours for progression and prognosis in vivo, we studied integrin expression (VLA-1 to VLA-6, CD18, CD51, CD61) on 10 naevi, 40 primary malignant melanomas, and 11 metastases by immunohistology using the APAAP technique. Evaluation was done by grouping the percentage of positive tumour cells in six categories. Statistical analysis (Wilcoxon rank test, Scheffe test) revealed significant differences in the expression of VLA-1 (P < 0.0001), VLA-2 (P = 0.0001), VLA-5 (P = 0.0093), VLA-6 (P = 0.0232), and CD61 (P = 0.0002) between naevi and primary melanomas. Comparing primary melanomas with metastases, a statistically significant decrease in the expression of VLA-1, VLA-2, and VLA-6 was detectable, as well as a significant increase in VLA-4 and VLA-5. There was no correlation between integrin expression and tumour type (superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma), regression and ulceration. Changes of VLA-1, VLA-4, and VLA-6 expression correlated with the tumour thickness of the primary melanoma, but only VLA-4 and VLA-6 expression on primary melanomas correlated significantly with the development of metastases (P = 0.024 and P = 0.001). These changes of integrin expression during tumour progression particularly, the data showing an increase of VLA-4, and a decrease of VLA-6 expression support the concept that integrins are a new additional set of prognostic markers which indicate predisposition to the development of metastases.
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PMID:Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours. 810 45

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


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