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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

First-trimester normal human trophoblast cells show some phenotypic similarities to malignant cells, e.g., rapid proliferation and ability to invade neighboring tissue, including basement membrane in situ, but do not have the ability for unlimited growth or metastasis. The present study examined whether the invasive ability of normal trophoblast cells is an intrinsic property of these cells, independent of the microenvironment provided by the pregnant uterus, and if so, whether they share some of the molecular mechanisms of invasion exercized by metastatic malignant cells. The ability of in vitro grown human trophoblast lines to invade an epithelium-free human amniotic membrane was measured from the temporal kinetics of retention of radioactivity within this membrane resulting from a penetration by 125I-iododeoxyuridine-labeled trophoblast cells. The magnitude of this invasion was compared to that of the highly metastatic human JAR-choriocarcinoma cell line and murine B16F10 melanoma line. Trophoblasts were found to share some of the same molecular mechanisms of invasion with the metastatic cell lines. Inhibitors of collagenase, plasmin, plasminogen, and plasminogen activators completely prevented invasion of the amnion by the trophoblast lines as well as by the metastatic JAR and B16F10 lines. Mersalyl, a compound known to activate collagenase, stimulated invasion by all cell lines tested, including under conditions in which plasmin activity was inhibited. In addition, trophoblasts produced significant levels of type IV collagenase and laminin, both of which appear to be important products of metastatic tumor cells required for basement membrane invasion. It may be concluded from these findings that the invasive property of first trimester human trophoblasts is genetically determined; that the magnitude of amnion invasion cannot differentiate between metastatic cell lines and invasive but nonmetastatic cell lines; and that invasiveness is not a sufficient prerequisite for metastatic ability.
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PMID:Normal nonmetastatic human trophoblast cells share in vitro invasive properties of malignant cells. 317 Jun 42

Homogenates from malignant tumors, obtained from surgery specimens or from transplants of Walker 256 carcinosarcoma in rats, contained an enzyme activity capable of degrading intact 3H-acetylated basement membranes from bovine lens. The enzyme activity from murine tumor was purified about 7500-fold by (NH4)2SO4 fractionation, ion exchange and gel chromatography. The apparent molecular weight of the purified enzyme was approximately 50,000. The rate of degradation of 3H-labelled basement membrane by the murine tumor enzyme was reduced by addition of excess type IV collagen, but not of excess type I, type III or type V collagen. These results suggested specificity of this enzyme for type IV collagen. Inhibitors of serine proteinases, thiol proteinases and soybean trypsin inhibitor were without effect on the enzyme activity. Chelators such as 1,10-phenanthroline or EDTA reduced the activity to control levels, indicating that the enzyme activity was due to a metalloproteinase. Chromatographic and electrophoretic separation of the enzymatic products from 3H-labelled basement membrane and type IV collagen indicated that the enzyme activity was due to a type IV collagenase. The use of basement membrane in the native physiological state as a substrate for the study of basement membrane-degrading activity by homogenates of solid malignant tumors offers an in vitro model for the investigation of the metastatic potential of these tumors.
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PMID:Degradation of intact basement membranes by human and murine tumor enzymes. 319 Nov 49

The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.
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PMID:Comparison of proteinase activities in squamous cell carcinoma, basal cell epithelioma, and seborrheic keratosis. 328 80

NIH/3T3 cells transfected with DNA from malignant human tumors produced experimental and spontaneous metastases in nude mice. In contrast, parent or spontaneously transformed NIH/3T3 cells failed to metastasize. The transfected clones contained either activated c-Harvey-ras or N-ras oncogenes. A representative clone (T71-17SA2) which was used to assess selected cellular and host factors relevant to the metastatic process produced lung metastases in 100% of the NIH nude mice recipients, secreted augmented levels of type IV collagenase, and invaded human amnion basement membrane in vitro. Expression of the metastatic phenotype was not related to decreased sensitivity to natural killer cells or macrophage-mediated cytotoxicity. Analysis of the cellular DNA from the T71-17SA2 transfectant and its corresponding metastases, both of which contained activated N-ras oncogenes, revealed a twofold increase in the N-ras-specific DNA sequences in the metastatic cells. Thus, transfection with human tumor DNA containing activated ras oncogenes can induce the complete metastatic phenotype in NIH/3T3 cells by a mechanism apparently unrelated to immune cell killing.
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PMID:NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice. 398 18

The ability of interferons to reduce cell proliferation in vitro and in vivo is a well-studied phenomenon. To extend such observations, the effect of interferons on the invasiveness in vitro of human malignant cells derived from a Ewing sarcoma was evaluated. Two related parameters were examined: (i) production of type IV (basement membrane) collagenase and (ii) penetration of human amnion basement membrane and collagenous stroma. After 6 days of treatment with crude fibroblast, leukocyte, or lymphoblastoid interferon at 100 units/ml in serum-free medium, type IV collagenase levels increased 2- to 4-fold per cell relative to those of untreated controls. With homogeneous fibroblast and lymphoblastoid interferons, a 2-fold elevation in type IV collagenase was detected after 2 days, with further increases, occasionally dramatic, occurring on the 4th and 6th day of treatment. The ability of Ewing sarcoma cells to invade human amnion connective tissue was measured after 6 days of treatment with various interferons. Relative to the behavior of untreated controls, crude leukocyte interferon, homogeneous lymphoblastoid interferon, and homogeneous fibroblast interferon at 100 units/ml augmented invasiveness 3-, 17- and 22-fold, respectively, when cells were allowed 4 days in which to traverse the amnion. When untreated cells were exposed simultaneously to the amnion and to homogeneous lymphoblastoid or fibroblast interferon, a 4- to 5-fold increase in invasiveness above control levels was observed in 2 days. These data emphasize the complexity of interferon-induced phenomena. In any overview, the effects of interferon on both the tumor cell and the host must be considered.
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PMID:Interferon enhancement of the invasive capacity of Ewing sarcoma cells in vitro. 618 Apr 34

Tumour invasion and metastasis is a complex process involving multiple interactions of tumour cells with host cellular and extracellular elements. Metastasizing tumour cells traverse basement membranes at many stages in the metastatic cascade. Immunohistology studies demonstrate that the basement membranes are defective in all human malignant epithelial neoplasms studied to date. The basement membrane is absent in regions of microinvasion and adjacent to actively invading tumour cells. In contrast, benign neoplasms retain a continuous basement membrane. This distinction may have diagnostic value in surgical pathology. Tumour cells are hypothesized to traverse basement membranes by a three-step process: attachment, local degradation of the basement membrane by type IV collagenase and other proteases, and locomotion. The first step may be mediated in part by specific cell surface receptors which bind to laminin in the basement membrane. The laminin receptor has been purified from a series of different human carcinomas. The receptor has an Mr of 67 000 and a binding coefficient of 2 nM. The content of unoccupied receptors is markedly augmented in invasive human breast cancer compared to benign controls.
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PMID:The laminin receptor and basement membrane dissolution: role in tumour metastasis. 624 Mar 91

In the initial phases of angiogenesis, endothelial cells must degrade and cross the vessel basement membrane, as do tumor cells during invasion and metastasis formation. Various metalloproteinases have been implicated in tumor cell invasion, in particular MMP-2 (72 kDa collagenase IV, gelatinase A), which has been demonstrated to be associated with tumor metastasis formation. Supernatants from AIDS-Kaposi sarcoma (KS) cells induce normal endothelial cells to invade through a reconstituted basement membrane (Matrigel) in vitro, which correlates with the angiogenic potential of KS cells in vivo. Here we demonstrate that two specific inhibitors of MMP-2, TIMP-2 and a peptide from the MMP-2 propeptide region (peptide 74), inhibit endothelial cell invasion induced by AIDS-KS cell supernatants. Smooth muscle cells were much less sensitive to these inhibitors. These data suggest that MMP-2 activation is a key event in endothelial cell invasion, the initial phase of tumor-associated neoangiogenesis. Inhibition of this enzyme could be an effective treatment for KS and tumor-associated angiogenesis.
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PMID:Inhibition of AIDS-Kaposi's sarcoma cell induced endothelial cell invasion by TIMP-2 and a synthetic peptide from the metalloproteinase propeptide: implications for an anti-angiogenic therapy. 753 74

UV radiation has been shown to play a role in the initiation of human cutaneous melanoma, but its role in the development of malignant melanoma to the metastatic state is not very well defined. Although previous studies have concentrated on the effect of UV-B on the host immune response, the effect of UV-B on the tumor cells was not elucidated. Here we show that UV-B can induce interleukin 8 (IL-8) mRNA and protein secretion in human cutaneous melanoma with negligible expression of IL-8. UV-B-induced IL-8 was constitutively expressed 60 days after irradiation in tumors implanted in mice. Induction of IL-8 was UV-B dose dependent and blocked by cyclohexamide, indicating that de novo protein synthesis is required for its expression. The UV-irradiated cells demonstrated enhanced tumorigenicity and metastatic potential in nude mice. The increase in tumorigenicity and metastatic ability could be explained by the increase in Mr 72,000 type IV collagenase activity and angiogenesis attributed to the induction of IL-8 after irradiation. The acquisition of the metastatic phenotype induced by UV-B could not be attributed to abnormalities in the p53 or MTS-1 (p16INK4) genes. To the best of our knowledge, this is the first report to show that UV-B can increase the aggressiveness of human cutaneous melanoma for growth and metastasis.
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PMID:Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8. 754 20

In vitro angiogenesis models suggest that new blood vessel formation requires the induction and secretion by endothelial cells of matrix metalloproteinases. These enzymes assist in the controlled proteolytic degradation of the surrounding extracellular matrix during blood vessel formation. The results of in vitro studies cannot be extrapolated directly to the process of in vivo angiogenesis because the type of matrix employed and the repertoire of enzymes secreted by cells in vivo differ dramatically from in vivo conditions. To investigate the in vivo role of matrix metalloproteinases in blood vessel development, we looked for the presence of these proteinases in endothelial cells involved in fetal angiogenesis and in neovascularization of certain invasive skin tumors using immunofluorescent staining. In fetal tissue, interstitial collagenase was present in both early microvessels developing from undifferentiated mesoderm and in microvessels involved in elongation and sprout formation from preexisting blood vessels. In aggressive skin tumors, i.e., morpheaform and recurrent basal cell carcinomas and squamous cell carcinomas, there was a marked increase in the number of collagenase-containing blood vessels, often extending into the tumor nests. Immunofluorescent staining failed to detect stromelysin, matrilysin, or gelatinase A and B (72- and 92-kDa type IV collagenases, respectively) in fetal or tumor blood vessels. These findings are consistent with the hypothesis that proteolytic degradation of the extracellular matrix is required for the formation of new blood vessels. Interstitial collagenase appears to play an important role in this process.
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PMID:Matrix metalloproteinases in blood vessel development in human fetal skin and in cutaneous tumors. 754 2

Studies suggest that the interplay between matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) is an important mediator of tumour invasion and metastasis. Using immunohistochemistry, 40 specimens of colorectal cancer were examined for the presence of TIMP-1 and the MMPs, stromelysin, gelatinases A and B and interstitial collagenase. Neither enzyme nor TIMP-1 was detected in histologically normal mucosa. Within malignant tissue, stromelysin and gelatinase A were conspicuously absent in tumor cells but were immunolocalized to the extracellular matrix and for gelatinase A also to peritumoural fibroblast-like cells. Gelatinase B was confined to polymorphonuclear leucocytes. Interstitial collagenase was not identified. TIMP-1 was present in only three of the 40 tumours within the malignant stroma. These observations suggest that the mesenchymal elements of colorectal carcinomas, by acting as a source of MMPs and TIMPs, may modulate tumour invasion.
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PMID:The distribution of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal cancer. 755 Dec 59


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