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)

The mechanisms by which tumor cells metastasize to bone are not well understood. We have investigated the role of the basement membrane glycoprotein, laminin, in bone metastasis, since antagonists to laminin have been shown to inhibit the formation of lung metastases. We studied the formation of osteolytic metastases caused by a human tumor which is known to cause osteolysis and hypercalcemia in nude mice. We found that tumor-bearing nude mice developed hypercalcemia, cachexia, and characteristic osteolytic lesions throughout the skeleton after injection of this human melanoma cell line (A375) into the left ventricle. When we gave injections to nude mice with A375 cells which had been exposed to C(YIGSR)3-NH2, a laminin-derived synthetic peptide containing three linear sequences of YIGSR with an amino-terminal cysteine which competes with laminin for its receptor, we found a decrease in the formation of detectable osteolytic bone metastases. The tumor cells were incubated with the antagonist and then inoculated into nude mice which were administered the antagonist i.p. Hypercalcemia and cachexia were also decreased in tumor-bearing mice treated with the laminin antagonist. In contrast, laminin itself increased the number of osteolytic bone metastases, as has been shown for other tumor cells. These data suggest that laminin plays a role in the formation of osteolytic bone metastases in this model and that laminin antagonists may be useful in the prevention of bone metastases in some human tumors.
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PMID:A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice. 139 44

We have previously established and characterized two monoclonal antibodies, 8F11 and 20A11, that recognize an Mr 44,000 membrane glycoprotein of metastatic murine colon 26 cells. Both monoclonal antibodies inhibit platelet aggregation induced by the tumor cells in vitro. In this report, the inhibitory effect of 8F11 on lung colonization of i.v.-inoculated tumor cells was examined. The i.v. administration of 8F11 suppressed lung colonization of NL-17, a highly metastatic variant of colon 26. Inhibition of NL-17 lung colonization by 8F11 was dose dependent with a maximum of 80% inhibition at a dose of 800 micrograms 8F11/mouse. 8F11 did not inhibit metastases at doses lower than 100 micrograms/mouse. Inhibition of pulmonary metastases by 8F11 was greatest when the antibody was administered 2 h before tumor inoculation. The effect was diminished when the antibody was given 2 h after tumor inoculation. The pulmonary retention of i.v.-inoculated radiolabeled NL-17 cells was decreased by 8F11. F(ab')2 fragments of 8F11 also effectively inhibited lung colonization by NL-17 cells, suggesting that mechanisms unrelated to immune-mediated destruction are involved. These results indicate that the monoclonal antibody 8F11 suppresses the lung colonization of NL-17 cells by interfering with the initial arrest of tumor cells in the lung vasculature through the inhibition of tumor cell-platelet interaction.
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PMID:Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell-induced platelet aggregation. 198 32

The 4F2 antigen is a cell-membrane glycoprotein which arises early in the G0-G1 phases of the cell cycle. This molecule is present in all established human cell lines and most malignant human cells. The authors used an indirect immunophosphatase method to study 50 squamous cell carcinomas of the larynx and ten lymph-node metastases, corresponding to six primary tumors, for 4F2 expression. The tumors showed several patterns of 4F2 staining which were correlated with different behaviors and prognoses of the neoplasms. Three different patterns (no staining, peripheral staining, and diffuse 4F2 expression) are described as are their relationships with metastatic behavior of the carcinomas. Tumors with metastases were found only in the third group (P = 0.0001). These results led to the following conclusions: (1) the 4F2 antigen is present in squamous cell carcinomas; (2) its distribution reflects the tumor-spreading pattern; and (3) it correlates with differentiation and metastatic behavior.
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PMID:Relationship of 4F2 antigen with local growth and metastatic potential of squamous cell carcinoma of the larynx. 220

The MUC18 antigen is an integral membrane glycoprotein of 113 kDa whose expression on primary human melanomas correlates with poor prognosis and the development of metastatic disease. MUC18 is expressed only sporadically in benign melanocytic nevi and thin primary melanomas that have a low probability of metastasizing. However, with increasing tumor thickness, MUC18 expression becomes more frequent and it is found on 80% of advanced primary tumors and metastases. MUC18-encoding cDNA clones were obtained by screening a human melanoma phage lambda expression library with monoclonal antibodies produced against the denatured antigen. The deduced sequence of 603 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The highest sequence similarity is with a group of nervous system cell adhesion molecules, which includes neural cell adhesion molecule (N-CAM). The close structural relationship with these molecules suggests that MUC18 may also be a developmentally regulated cell adhesion molecule.
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PMID:MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. 260 81

A monoclonal mouse antibody (MoHG) was produced using in vitro cultured AH66R tumor cells treated with cholesteryl hemisuccinate as an immunogen. The antibody identified a 90 kd membrane glycoprotein (HG-90) which is expressed on in vitro cultured hepatoma cell lines AH66 and AH66R. A monoclonal antibody was prepared to the anthracycline drug daunomycin, and it also reacted with adriamycin. A fusion was made of the hybridoma HG-90 with the hybridoma which recognized daunomycin/adriamycin. This bispecific hybridoma A8C recognized both determinants. We studied the therapeutic effect of the A8C bispecific antibody with adriamycin treatment and compared it to the effect of the bispecific antibody to which adriamycin had been conjugated via an albumin (Alb) bridge. The therapy model used was the tumor AH66R in Donryu rats. Tumor bearing rats had their subcutaneous tumors resected on day 10, a time when distant metastases were present. After the surgical resection of the tumor the rats were injected intravenously for two cycles with the bispecific antibodies, followed by the administration of adriamycin (ADR) or MoHG.Alb.ADR conjugates. A slight therapeutic effect occurred with either MoHG or ADR alone but treatment with the bispecific antibody followed by the administration of ADR or with the MoHG.Alb.ADR conjugates significantly prolonged survival, with 60% of the treated animals being "tumor free" when sacrificed on day 80. Lower serum concentrations of alphafetoprotein were observed with the bispecific antibody and drug treatment. This suggests that the bispecific antibody/drug treatment is potentially more beneficial in the suppression of distant metastases than the MoHG.Alb.ADR conjugate. This may be due to an increase in the local drug concentration of unmodified adriamycin.
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PMID:The effect of bispecific monoclonal antibody recognizing both hepatoma-specific membrane glycoprotein and anthracycline drugs on the metastatic growth of hepatoma AH66. 278 98

Cancer invasion and metastases is a complex multi-step process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA in a variety of human carcinoma cells correlated with the number of laminin receptors on the surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases by employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor, resulting in a profound (greater than 100 x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
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PMID:Biochemical mechanisms of tumor invasion and metastasis. 283 60

Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
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PMID:Biochemical mechanisms of tumor invasion and metastases. 283 81

Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
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PMID:Biochemical mechanisms of tumor invasion and metastases. 285 25

Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20-, and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony-forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR-resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity.
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PMID:Characterization in vitro and in vivo of progressively adriamycin-resistant B16-BL6 mouse melanoma cells. 288 31

Tumor cell variants which grow adherent to a plastic surface could be isolated in a reproducible way from the high metastatic tumor cell line ESb which grows in a suspension culture. This occurred when starting selection from the uncloned parental line as well as from a freshly derived non-adhesive subclone. The variants showed changes in their karyotype. These were quantitative (tetraploidization) and qualitative (single chromosome aberrations involving the chromosomes 12 and 17 and a marker MX-7). Phenotypic cell surface changes were documented in vitro by immunofluorescence using a monoclonal antibody (mAb 12-15) directed against a distinct plasma membrane glycoprotein of 60-69kD (gp 60-69). The expression of gp 60-69 increased with time of selection for adherence to plastic surface. The adherent cells showed in all cases a greatly reduced overall malignancy as seen by a prolonged survival time of respective tumor bearing animals compared with the suspension growing parental cells.
Clin Exp Metastasis
PMID:Generation of adhesive tumor variants: chromosomal changes, reduction in malignancy and increased expression of a distinct membrane glycoprotein. 304 58


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