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)

We have previously shown that differences in cell surface carbohydrates can be detected in related murine tumor lines of varying metastatic capacity using plant lectins such as soybean agglutinin (SBA) or Vicia villosa (VV) but not concanavalin A (ConA). Here we show that weakly metastatic Eb cells bind SBA via four glycoproteins and one GL2-like glycolipid. The major high-affinity SBA binding component of weakly metastatic ESb-MP cells was a glycoprotein of 210-220 kd. Highly metastatic ESb cells also expressed this protein but the oligosaccharide side chains were altered in such a way that SBA-binding was completely lost while ConA and peanut agglutinin (PNA) binding remained similar. Quantitative binding studies using iodinated lectins indicated that SBA binding of ESb cells could only be detected at lectin concentrations greater than 75 micrograms/ml. The role of altered carbohydrates in metastasis is discussed.
Clin Exp Metastasis
PMID:Molecular identification of lectin binding sites differentiating related low and high metastatic murine lymphomas. 333 81

Metastatic variants of the B16 melanoma displaying high experimental metastatic potential have been shown to express high levels of a 72,000-dalton glycoprotein (Met-72) on their cell surface (Kimura AK, Xiang J: J Nat Can Inst 76:1247-1253, 1986). Monoclonal antibodies (MoAb) directed against the Met-72 determinant have been used in this study as immunohistochemical reagents on preparations of fresh B16 melanoma tumors and their metastases. These immunohistochemical analyses have utilized frozen sections, impression smears, and cytospin preparations of fresh tumors harvested at various time points during tumor growth, to view the presence and location of Met-72-positive metastatic variants within tumor masses. Biotinylated anti-Met-72 MoAbs were reacted with freshly dissociated tumor cells from a B16 melanoma ovarian metastasis. These cells were then reacted with fluorescein isothiocyanate (FITC)-streptavidin and analyzed by flow cytometry. A discrete population of positively staining cells was detected and isolated by cell sorting techniques. Met-72-positive cells were then cloned and reanalyzed after several weeks of in vitro expansion and found to have high experimental metastatic potential to ovaries. Frozen sections of subcutaneous tumors and their metastases were analyzed by immunoperoxidase techniques. A consistent finding in these studies has been that the few tumor cells which showed high intensity of Met-72 staining were positioned perivascularly and at the invading front of B16 melanoma tumors.
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PMID:Isolation and visualization of Met-72-positive, metastatic variants present in B16 melanoma tumor masses. 337 5

To evaluate the value of intact hCG, the beta-subunit of hCG and the common alpha-subunit of the glycoprotein hormones as tumour markers in patients with gastrinomas, we investigated 30 patients with the Zollinger-Ellison syndrome. Fifty-seven percent of the patients with malignant disease (N = 7) and 45% of those with active and apparently benign disease (N = 20) had raised values of circulating alpha-subunit. Detectable levels of hCG or hCG-beta were found in 7 patients of whom 4 had malignant disease. Radical tumour resection in 2 patients resulted in normalisation of elevated levels of alpha-subunit, and in one patient who developed metastases, the alpha-subunit values became elevated simultaneously. By chromatographic studies we found that the alpha-subunit-like reacting substance in serum eluted as the normal free alpha-subunit in 8 patients, but in one patient with metastatic disease we found evidence for production of a larger molecular form of alpha-subunit. The results indicate that the common alpha-subunit is a valuable tumour marker in patients with gastrinomas, whereas hCG-beta is only seldomly elevated. Single estimates of any of the hormonal fragments seem not to relate with malignancy, whereas a rise in alpha-subunit concentration in some patients may be related to the development of malignancy.
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PMID:Levels of alpha-subunits of gonadotropins can be increased in Zollinger-Ellison syndrome, both in patients with malignant tumours and with apparently benign disease. 338 44

In the present study, we report a more detailed biochemical analysis of the B16 melanoma, metastasis-associated, Met-72 antigen. Specifically, we have examined (1) the molecular forms of Met-72 isolated during synthesis, surface expression and 'shedding' and (2) the cell-surface expression of Met-72 during the cell cycle. These experiments show that the 72 kD species originally described has an isoelectric point of between 6.3 and 6.9, but is the desialylated derivative of an 83 kD native molecule whose isoelectric point ranges between pH 4.9 and 5.6. In addition, a 90 kD glycoprotein doublet was immunoprecipitated from biosynthetically labelled B16 melanoma cells, but does not appear to be a precursor of the 83 kD or 72 kD molecule. These findings have led us to interchangeably use the terminology Met-72 and Met 72/83. The latter terminology more accurately describes the physical forms which can be identified by different labelling procedures. When culture supernatants from 3H-leucine labelled cells were subjected to anti-Met-72 immunoprecipitation, a 35 kD species was identified as a possible 'shed' product of these cells. Met-72/83 expression during the cell cycle was analyzed by flow cytometry and found not to be restricted to any particular stage. In addition, experiments were performed to determine whether low levels of Met-72 expression on poorly metastatic B16 melanomal clones was a direct result of low levels of synthesis, or if other control mechanisms regulated intracellular pools of Met-72 prior to cell-surface expression.
Clin Exp Metastasis
PMID:Synthesis and expression of metastasis-associated, Met-72/83 antigens. 340 61

Fibronectin, a large glycoprotein found in soluble form in plasma and in insoluble form in connective tissue matrices, has been implicated in cell-to-cell and cell-to-substratum interactions, inflammation and tissue repair, phagocytosis, hemostasis, and oncogenic cell transformation. Because fibronectin concentration is diminished or lacking on cell surfaces of many transformed cell lines and because decreased concentration of plasma fibronectin is associated with suboptimal mononuclear phagocyte system function and host defense, plasma fibronectin concentration was evaluated in 119 dogs with various forms of neoplasia. Included were 43 dogs with neoplasia of the skin and soft tissue, 18 with gastrointestinal tract neoplasia, 29 with mammary gland neoplasia, and 29 with various other types of neoplasia. Of the dogs studied, 44 (37%) had evidence of metastatic disease. This group had fibronectin concentration that differed significantly (P less than 0.01) from the plasma fibronectin concentration reference interval. Within this group, 9 dogs (20% of this group) had plasma fibronectin values within the reference interval, 33 (75%) had significantly (P less than 0.01) lower values than the reference interval, and 2 (5%) had significantly (P less than 0.01) higher values than the reference interval. These data suggested that fibronectin concentration determination, when results are abnormal, may be of diagnostic and prognostic interest.
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PMID:Plasma fibronectin concentration associated with various types of canine neoplasia. 342 25

A panel of monoclonal antibodies was tested immunohistochemically to determine the utility of such reagents in distinguishing among metastatic carcinoma, lymphoma, leukemia and primary brain tumors. The monoclonal antibodies used were: (1) a cocktail comprised of three anti-glial fibrillary acidic protein antibodies (alpha-GFAP); (2) UJ13A, a panneuroectodermal antibody; (3) B72.3, which recognizes a carcinoma-distinctive tumor-associated glycoprotein complex; and (4) 2D1, a pan-leukocyte antibody. Fifty-three specimens (21 cerebrospinal fluids, 1 ventricular fluid, 2 brain cyst fluids, 12 needle washings, 15 imprints, 1 subdural fluid and 1 post-shunt fluid) were obtained from 21 gliomas, 2 meningiomas, 1 pineoblastoma, 11 metastatic tumors, 3 lymphomas, 1 leukemia and 14 cases without tumor. alpha-GFAP stained all 21 gliomas and 5 of 5 cases containing reactive brain fragments. UJ13A had a reactivity pattern similar to that of alpha-GFAP, but also stained the meningiomas, pineoblastoma, oat-cell carcinoma and embryonal rhabdomyosarcoma. B72.3 stained all adenocarcinomas and the large-cell carcinoma. 2D1 stained lymphoma and leukemia, all inflammatory cells and 4 of 12 glioblastomas. Although no single antibody was diagnostic of a specific tumor type, this panel accurately differentiated among most primary brain tumors, metastases, leukemias and lymphomas.
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PMID:The use of a panel of monoclonal antibodies in the evaluation of cytologic specimens from the central nervous system. 342 42

Three lines of B16 melanoma cells (B16-F1, B16-F10 and B16-BL6) were examined for motility in the micropore filter assay and for synthesis in culture of the basal lamina glycoprotein laminin. All three lines synthesized laminin as judged by the incorporation of [35S]methionine into immunoreactive laminin and secreted (or shed) laminin into the culture medium as indicated by biosynthetic labeling studies and enzyme-linked immunosorbent assays. Immunoreactive laminin was also seen on the surface of the cells as indicated by immunofluorescence staining and by complement-mediated killing. Analysis of [35S]methionine-labeled laminin immunoprecipitates by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) both with and without reduction of intersubunit disulfide bonds revealed that all three cell lines produced a similar array of laminin forms, and that the Mr = 950 kD laminin molecule (but not the uncombined subunits) was secreted into the culture medium. Laminin biosynthesis appeared to be limited by the availability of the Mr = 400 kD A subunit as shown by the intracellular accumulation of excess B subunit in the form of uncombined B subunit (Mr = 200 kD) and as a disulfide-linked B dimer (Mr = 400 kD). The motility of all three cell lines was stimulated four- to five-fold by the addition of either exogenous laminin from the EHS sarcoma or culture medium from the B16 cells containing the secreted laminin. The stimulated motility was inhibited by antilaminin serum. These observations suggest that the laminin synthesized by the B16 melanoma cells themselves may facilitate their motility.
Clin Exp Metastasis
PMID:Laminin production by murine melanoma cells: possible involvement in cell motility. 353 34

Sulfated macromolecules synthesized in tumor and mucosa tissues derived from colorectal cancer patients were labeled with [35S]sulfate and separated into two fractions on DEAE-Sephacel: the slightly acidic peak (peak I) was eluted with 0.2 M NaCl and the highly acidic peak (peak II) was eluted with 0.5 M NaCl. A total of 40 specimens, which included primary colon cancer, liver metastases, and normal mucosa obtained at surgery (16 patients), were examined regarding the amount of peak I and peak II. The amount of peak I significantly decreased in the order of normal mucosa greater than primary tumors greater than metastases, while the amount of peak II did not significantly change among the tissues. Peak I was mostly resistant to chondroitinase ABC and nitrous acid treatment under acidic conditions, whereas combined chondroitinase-sensitive materials and nitrous acid-sensitive materials were greater than 80% of the radioactivity in peak II. The major radioactive component of peak I migrated at a position corresponding to Mr greater than 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and became Mr less than 40,000 after alkaline borohydride treatment. The major component of peak I was likely to be a sulfated glycoprotein containing sulfate groups on alkaline labile carbohydrate chains. Peak II consisted of a mixture of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans. Differential incorporation of [35S]sulfate into peak I among normal mucosa, primary colon carcinoma, and colon carcinoma metastasis was observed. Therefore, decreased peak I production may be a biochemical change associated with colorectal cancer progression and metastasis.
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PMID:Differential production of high molecular weight sulfated glycoproteins in normal colonic mucosa, primary colon carcinoma, and metastases. 356

The growth and metastatic behavior of several human tumor lines grown in adult nude mice, nude mice pretreated with antiserum against asialo GM1 glycoprotein, and beige nude mice were studied. The cell lines were all injected s.c. and i.v. A human colon carcinoma line was also injected into the spleen, and two human renal carcinoma lines were injected into renal subcapsule. All the tumor lines grew as fast or faster in adult nude mice compared with beige nude mice. There were no discernible differences in the production of experimental lung metastasis among the three groups of mice, but human colorectal carcinoma cells and human renal carcinoma cells produced more metastases in nude mice than in beige nude mice after intrasplenic or renal subcapsule injection, respectively. In vitro cytotoxicity assays confirmed that adult nude mice had high levels of natural killer (NK) cell activity whereas nude mice pretreated with anti-asialo GM1 serum and beige nude mice did not. The in vitro NK cell activity of nude mice was demonstrable against mouse lymphoma cells but not against human leukemia cells which were sensitive to lysis by human NK cells. These results suggest that the implantation of human tumor cells into beige nude mice, which are deficient in NK cell activity does not provide an advantageous model for the study of growth and metastasis of human neoplasms.
Clin Exp Metastasis
PMID:Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice. 359 71

The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutic agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50% inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50% growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.
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PMID:Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. 366 87


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