Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined normal human placenta for an immunologic function by measuring the release of soluble inhibitory factor (SIF). SIF is a product of normal T lymphocytes and of the JEG-3 choriocarcinoma cell line, and blocks proliferative and antibody-producing responses of mononuclear cells. SIF can be further characterized by a noncovalently linked subcomponent, lipid suppressor substance. The villous surfaces of six normal human placentae were digested with collagenase to obtain a population of predominantly multinucleated giant cells. These cells were maintained in standard culture for 5 days after which the cell-free conditioned culture medium was assayed for SIF content by measuring suppression of [3H]thymidine incorporation into lymphocytes stimulated by low-dose phytohemagglutinin. Undiluted placental SIF induced 88% inhibition of this response (p less than 0.001). The placental SIF was found to contain lipid suppressor substance, as does SIF from mononuclear cells. We determined this by thin-layer chromatography where a peak of suppressive activity occurred at Rf 0.32 [( 3H]thymidine incorporation reduced from 21810 +/- 308 to 4121 +/- 214 cpm); this is the position on thin-layer chromatography to which mononuclear cell lipid suppressor substance migrates. Ion exchange chromatography comparing the elution patterns of lymphocyte-SIF and placental-SIF indicated that both eluted in the fraction of 40-50 mM PO4 means buffer, further suggesting identity between these two substances. SIF from placental and lymphocyte sources functioned by inducing the presence of suppressor cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human placental cells that regulate lymphocyte function. 296 36

The chick chorioallantoic membrane (CAM) was used as an assay system to examine the invasive potential of human choriocarcinoma cell lines. When 5 X 10(6) cells were inoculated into the CAM at the 10th day of postfertilization, three of eight cell lines formed extensively invasive tumors within the CAM. A tendency to correlation between the tumorigenic potential of cell lines in hamster cheek pouches and their invasive potential in the CAM was noted. In addition, the invasive capacity of cell lines correlated well with the amount of collagenase but did not correlate with the amount of plasminogen activator or cathepsin B secreted by them. It is concluded that a heterogeneity of invasive potential in the CAM exists among human choriocarcinoma cell lines and the role of the collagenase secreted by them is suggested.
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PMID:Invasion potential of human choriocarcinoma cell lines and the role of lytic enzymes. 299 58

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

Cytotrophoblasts (from term placentae) and cells from the choriocarcinoma cell line JAr were cultivated either separately or in co-culture for 72 h. RNA was isolated from the cell cultures and Northern blots were developed using equal amounts of RNA. The RNA was hybridized with cDNA probes for CG alpha, CG beta and hPL. Corresponding m-RNAs were detected in the three RNAs except for hPL m-RNA which was absent from JAr cells RNA. The abundance of CG alpha and CG beta m-RNA in the RNA of the co-culture was higher than their accumulative abundances in the RNAs from cytotrophoblasts and JAr cells cultured alone and the abundance of hPL m-RNA in the RNA of the co-cultures was as high as that in the RNA from cytotrophoblasts cultured alone. On the basis of previous findings (Hochberg et al, 1991), it can be assumed that the cytotrophoblasts in the co-cultures are responsible for the increase in hormonal m-RNA production. It could be calculated that the abundances of the CG alpha, CG beta and hPL m-RNAs in the RNA which originated in the cytotrophoblast nuclei were 20, 100 and 10-fold higher respectively in the co-culture compared to those in the culture of cytotrophoblasts. This effect is limited to certain genes only as the concentration of the 92kD collagenase m-RNA and uPA (urokinase type plasminogen activator) m-RNA, which are both produced in cytotrophoblasts to a much higher extent than in JAr cells, and are not increased by cultivating the cytotrophoblasts with JAr cells in co-culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction between choriocarcinoma cell line (JAr) and human cytotrophoblasts in vitro. 768 96

Impaired trophoblastic invasion and proliferation have been implicated in the pathogenesis of eclampsia, pre-eclampsia, spontaneous abortions and intra-uterine growth retardation (IUGR). First trimester trophoblast cells (which do not grow in culture) and choriocarcinoma (BeWo) (which grow spontaneously, and are used as a model for proliferating trophoblast) were incubated with interleukin-1 beta (IL-1 beta). BeWo cell growth was decreased dose-dependently by exogenous IL-1 beta at concentrations of 100-1000 pg/ml. This effect was first detected after 24 h of incubation with IL-1 beta, and persisted for up to 96 h of culture. In contrast, trophoblast cells isolated from first trimester placental tissue showed no growth response when stimulated with IL-1 beta. The levels of active interstitial collagenase produced by BeWo cells were increased by IL-1 beta (100-1000 pg/ml), which paralleled the decrease in cell growth. First trimester trophoblast cells produced lower levels of collagenase and this was not affected by incubation of the cells by IL-1 beta. These results indicate that IL-1 beta may regulate placental development, but further development of culture systems for first trimester trophoblast will be needed before this result can be confirmed.
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PMID:Regulation by interleukin-1 beta of growth and collagenase production by choriocarcinoma cells. 820 67