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

Three distinct dissemination-related phenotypes have been distinguished among cell subpopulations of the mouse B16 melanoma: tumorigenicity, spontaneous metastasis from subcutaneous tumors, and organ colonization following intravenous injection of cells. From a progenitor clone (G3) of tumorigenic but nonmetastatic and noncolonizing (null) cells that underwent phenotypic diversification in vitro and in vivo, 4 subclones were obtained: G3.5 (culture-generated metastatic), G3.12 (tumor-generated metastatic), G3.15 (culture-generated null), and G3.26 (tumor-generated colonizing). The growth potentials of the parent clone and derived subclones were investigated comparatively in in vivo assays (tumorigenicity, tumor growth rate, and lung colonization potential), monolayer culture assays (generation time, saturation density, clonogenicity, and rate of detachment by trypsin), and in soft agar. In overall growth potential, G3.26 greater than G3.12 greater than G3, G3.5 greater than G3.15. These results indicate that metastatic populations of the B16 melanoma are not the most rapidly and effectively growing cells obtainable from that tumor.
Invasion Metastasis 1985
PMID:Growth characteristics of clonal cell populations constituting a B16 melanoma metastasis model system. 388 9

The levels of a trypsin-like neutral proteinase present on tumor cell surface (SNP) have been determined in P388, L1210, TLX5 leukemias, and in two lines of Lewis lung carcinoma having different metastatic potential. No correlation between metastatic potential and SNP levels of the tumor lines examined has been observed, and metastasis depression by antimetastatic and antineoplastic drugs was not accompanied by SNP inhibition. These data seem to support the view that metastatic potential is not necessarily related to tumor proteinase levels.
Invasion Metastasis 1985
PMID:Tumor cell metastasis and surface neutral proteinase: effects of antimetastatic and antitumor drugs. 390 87

Platelet-aggregating and thrombin-generating activities of B16 and 3LL cells were inhibited by trypsin, phospholipase A2 and by heating, but not by neuraminidase. It was confirmed that the platelet aggregation effect of these cells is due to thrombin generation. The lung-colonizing ability of treated cells injected intravenously was directly proportional to the ability to generate thrombin and to aggregate platelets. These results suggest that B16 and 3LL cells aggregate platelets through thrombin generation probably via their heat-labile surface lipoprotein, and that emboli composed of platelets, fibrin, and tumor cells may aid further the metastatic process.
Invasion Metastasis 1986
PMID:Platelet-aggregating activities of metastasizing tumor cells. IV. Effects of cell surface modification on thrombin generation, platelet aggregation and subsequent lung colonization. 394 Oct 29

Three human cell lines from adenocarcinomas of the extrahepatic biliary tract were established in permanent tissue culture. Mz-ChA-1 and Mz-ChA-2 were cultured from mechanically dissociated gallbladder adenocarcinoma metastases and SK-ChA-1 was grown from malignant ascites of a patient with primary adenocarcinoma of the extrahepatic biliary tree. Cell doubling times in tissue culture are 3-4 days for Mz-ChA-1 and approximately 2 days for Mz-ChA-2 and SK-ChA-1. All three tumour cell lines were successfully transplanted to nude mice, inducing progressive tumour growth. Histologically, nude mouse tumours resembled the original adenocarcinomas. In vitro formation of gland-like structures were regularly seen in Mz-ChA-1 and Mz-ChA-2 but only occasionally in SK-ChA-1. All three cell lines formed contacts through interdigitating processes with desmosomes and junctional complexes. On scanning electron microscopy, an abundance of microvilli was seen at the cell surfaces. Chromosome analyses of all three tumour cell lines showed a wide range of numerical abnormalities and presence of marker chromosomes. Mz-ChA-1 appears to be highly differentiated with cells producing mucus. Mz-ChA-2 synthesizes components of complement C2, C3 and C5, while Mz-ChA-1 and SK-ChA-1 produce only C3 in detectable quantities. In addition, Mz-ChA-2 supernatants are positive for ferritin and alpha 1-fetoprotein, but not CEA; while Mz-ChA-1 and SK-ChA-1 produce only CEA. Supernatants of all three cell lines are positive for N-acetyl neuraminic acid (NANA), phosphohexoisomerase (PHI) and LDH, and negative for alpha 2-macroglobulin, alpha 1-anti-trypsin, gamma-GT, AP, coeruloplasmin, haptoglobin and albumin. A high cloning efficiency renders these new tumour cell lines suitable for continued studies on clonal heterogeneity in malignant tumours. The establishment of these cell lines in tissue culture facilitates further studies on the biology of upper gastrointestinal tract cancer in man.
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PMID:Biliary adenocarcinoma. Characterisation of three new human tumor cell lines. 405 57

Two clonal tumor subpopulations (designated as A and D) obtained originally from a heterogeneous human colon adenocarcinoma (DLD-1) were used to produce xenograft solid tumors in nude mice. First, disaggregation studies were performed to determine the optimal choice of enzyme and time of dissociation for the pure A and D neoplasms, using cell yield (cells/mg/min) and colony forming efficiency (CFE) assays. The enzymes investigated were: 0.5 or 0.2% trypsin, and two cocktails containing pronase (0.5 or 0.05%), collagenase (0.02%), and DNAse I (0.02%). For the 0.5% trypsin treatments, the cell yield from A and D tumor fragments increased until about 30 min, at which time a plateau in cell yield was reached. A plateau in CFE was also reached at this time. In contrast, the cell yields for the 0.2% trypsin treatment did not reach a plateau within the time of the dissociation (120 min), and the CFEs were lower than with the 0.5% trypsin. Whereas no differences in cell yield or CFE were found between the enzyme cocktail studies (0.5% trypsin vs. 0.05% pronase), the cell yield and the CFE from the clone D carcinomas were significantly less than that found with the 0.5% trypsin (the cell yield and CFE from clone A tumors were identical for 0.5% trypsin or enzyme cocktail). These data indicate that, while these clonal neoplasms have somewhat different responses to enzyme disaggregation, it is possible to select an enzyme treatment and treatment time that is appropriate for use on both A and D tumors (i.e., 0.5% trypsin). After determination of an acceptable enzyme procedure, 'reconstructed' heterogeneous tumors produced from an initial injection bolus of 50% clone A and 50% clone D cells were disaggregated as a function of time (days 12-83 postinjection). Over this period, we found that the cell yield decreased exponentially, with a half-time (T1/2) of 20.5 +/- 7.3 days (95% confidence limits), with a maximum extrapolated cell yield at time zero of about 1.2 X 10(5) cells/mg. The CFE was essentially constant over the duration of the assay period. Moreover, it was found that the percentage of clone A cells appeared to decrease exponentially (T1/2 = 20.5 +/- 11.5 days, 95% confidence limits) until about 40 days postinjection. After this time an equilibrium mixture consisting of about 10% clone A cells and 90% clone D cells was reached.(ABSTRACT TRUNCATED AT 400 WORDS)
Invasion Metastasis 1985
PMID:Disaggregation studies of xenograft solid tumors grown from pure or admixed clonal subpopulations from a heterogeneous human colon adenocarcinoma. 406 5

A primary subcutaneous tumour of low spontaneous metastatic capacity, produced after inoculation of Herpes-virus hominis type-2-transformed hamster fibroblasts (parent line) and two in vivo derived highly metastatic lung deposits (Met A and Met B) were karyotyped and compared after trypsin G-banding. The parent line was cytogenetically heterogeneous with a modal chromosome number of 74. However, a number of cells were of a higher ploidy level. A large variation in both numerical and structural abnormalities was observed, the chromosome rearrangements were often complex and unstable, but all the cells contained a theme of common marker chromosomes. Met A and Met B were near diploid (mean chromosome numbers 42 and 44 respectively) with a low level of tetraploid cells. They shared many chromosome rearrangements but could be readily distinguished by an additional translocation unique to Met A. Cytogenetic homogeneity within and between metastases suggested that they were of monoclonal origin and had been derived from a karyotypically similar subpopulation within the parent tumour. We were unable to detect such cells in the parent line; thus, their numbers within the parent tumour were likely to be low. Metastasis, therefore, has been highly selective, depending on the particular phenotypic properties of Met A and Met B. All cells of the parent and metastatic lines have homogeneously staining regions (HSR) and abnormalities of chromosomes 15 (C15) which may be important in tumorigenesis. In addition, Met A and Met B cells have a number of chromosome rearrangements [translocations, deletions and a double minute chromosome (DM)] not present in the parent cells. They are retained at a high frequency in the cells of Met A and Met B and thus it seems likely that the metastatic phenotype is associated with one or more of these chromosome aberrations.
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PMID:Non-random chromosome changes in a herpes-virus-transformed Syrian hamster cell line and its metastatic derivatives. 609 77

After incubation with an encephalitogenic factor from human (HEF) or rat (REF) brain, lymphocytes of Fischer 344 rats bearing a spontaneous mammary adenocarcinoma produced a soluble substance which reduced the mobility of tanned sheep red blood cells in the electrophoretic mobility test (EMT). For studying the kinetics of this lymphocyte response, 6 X 10(5) tumor cells were injected into the hind footpad. In correlation with time and tumor size, one was able to influence the appearance of metastases by amputation of the leg. As early as 16 hours after inoculation of tumor cells, sensitivity of lymphocytes against HEF and a KCl-extract of the tumor could be shown in the EMT. It decreased on days 2 and 5, but was still seen until the day of amputation. Rats without metastases showed sensitivity up to four weeks after amputation and then returned to normal levels. Rats with metastases showed sensitivity until death at about seven weeks later. With the use of Amicon membranes, Sephadex G-50, and ion-exchange chromatography, a protein could be isolated from human basic myelin extract with a molecular weight of about 16,000-20,000 daltons. It had no direct influence on the EIC by itself, but after incubation with lymphocytes from tumor-bearing rats it evoked the production of a slowing substance. Using Sephadex G-100, the slowing substance appeared in the region in front of BSA indicating a molecular weight of greater than 80,000 daltons. It was heat-stable for 30 min at 56 degrees C and was sensitive to trypsin.
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PMID:Electrophoretic mobility test (EMT): studies on lymphocyte response and mechanism of the test using a rat tumor model. 616 95

To determine the point at which transformation of the germ cell occurs during meiosis in nonseminomatous testicular cancer, the sex chromosome compositions of 15 cell lines derived from primary tumors or metastases of 12 patients with testicular cancer were analyzed by trypsin G-banding analysis and Y-body staining. The simultaneous existence of both X- and Y-chromosomes in a single cell has been confirmed in 14 cell lines. This suggests that transformation of the cell occurs before the first meiotic division because it is known that segregation of X- and Y-chromosomes occurs during the first meiotic division. An incidental finding was the presence of Barr bodies in some cell lines containing more than one X-chromosome, which is consistent with the known primitive nature of testicular cancer and its ability to differentiate independently from the male host.
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PMID:Cytogenetic evidence for premeiotic transformation of human testicular cancers. 616 59

Because tumor-induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor-induced platelet aggregation as well as the effect of various anti-platelets agents. Two mechanisms for tumor-induced platelets aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo-lipo-protein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phospholipid component of the tumor membrane. We now report a new mechanism of tumor-induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen-induced metastatic murine colon carcinoma, CT26. These tumors do not require cell-surface sialic acid or serum complement as does the first mechanism. They do not require cell-surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin-sensitive surface protein for activity. The ability of the thrombin-generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin-competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacyclin, 6-keto-PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor-induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti-platelet pharmacologic agents. Sensitivity to anti-platelet agents correlates with the mechanism by which tumor cells aggregate platelets.
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PMID:A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases. 629 77

Three types of Morris hepatoma: 7288C, 5123tc, and 9618A were assessed for their ability to grow and produce metastases in the lungs of male buffalo rats. Hepatoma 7288 formed metastatic growths more rapidly than 5123, while 9618 did not form metastatic growths in the lung at all. Cells from the same three hepatomas were then assessed for their ability to aggregate homotypically in vitro. This was used as a measure of potential for detachment from the site of primary growth in vivo, one of the critical steps in metastasis. The results were that 9618 aggregated more effectively than 5123 and 7288 did not aggregate homotypically. Thus, the ability to metastasize and the ability to aggregate homotypically were inversely related in these three tumors, with the most metastatic tumor, 7288, hardly aggregating at all. Was the ability of hepatoma 9618 to aggregate homotypically and the inability of hepatoma 7288 to do so a characteristic of the plasma membrane? Plasma membranes either from the tumor which aggregated best, 9618, or from the liver of non-tumorous neonatal buffalo rats were fused into the surface of the 7288 cells. Either fusion conferred the ability to aggregate on the previously non-aggregating metastatic hepatoma cells. In contrast, fusion of plasma membranes from hepatoma 7288 into 9618 cells failed to affect their ability to aggregate homotypically. The aggregation-conferring effect required actual fusion of the donor membrane, was dependent on the amount of membrane fused and was sensitive to treatment of the donor plasma membranes with trypsin. The results are interpreted as suggesting the presence of homotypic aggregation materials, probably proteins, in the plasma membranes of non-metastatic cells. These may be reduced or absent in the membrane of the highly metastatic hepatomas.
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PMID:Increase in homotypic aggregation of metastatic Morris hepatoma cells after fusion with membranes from non-metastatic cells. 631 6


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