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L M Matrisian

Publications and source records attributed to L M Matrisian.

121 records · Page 7Linked to original sources
PubMed1983

Binding of epidermal growth factor in rat pancreatic acini.

Specific, saturable EGF receptors were demonstrated in isolated rat pancreatic acini. Binding of EGF to these receptors was one-half maximal at 20 min and maximal at 120 min. Scatchard analyses revealed a single order of binding sites with a Kd of 4.90 nM. Following binding, EGF was rapidly internalized and converted to two acidic species. EGF did not alter either basal amylase release or the rate of [3H]phenylalanine incorporation into TCA-precipitable protein. The finding of high affinity EGF receptors in pancreatic acinar cells supports the hypothesis that EGF participates in the long-term regulation of pancreatic exocrine function.

Animals↗
PubMed1982

Effect of epidermal growth factor on clonogenic growth of primary human tumor cells.

The effect of EGF on the soft agar colony-forming ability of fresh human tumor cells was assessed in 40 specimens obtained from various types of carcinoma including those of the breast, endometrium ovary, and other sites. Cells from four established human tumor cell lines (three breast and one endometrial) were also included in this study. The results showed that addition of EGF at a concentration of 50 ng/ml resulted in a 50% higher cloning efficiency in soft agar in 40% of the samples of fresh human tumors. When cells from tumor cell lines were plated in semi-solid medium containing EGF, the number of colonies formed was at least twice as high as controls. Cells from fresh tumor biopsies were assayed for EGF receptors to determine whether the correlation between the proliferative response in EGF-supplemented semi-solid medium as compared to control could be related to the number of EGF receptors present on the cells. Specific receptors for EGF were detected by using radioiodinated EGF in early-passage cell cultures from some of the tumors tested for clonogenicity. The number of receptors ranged from 0.3 to 3.27 X 10(5) per cell. Cells from two melanoma specimens possessed less than 0.3 X 10(3) EGF receptors per cell. We found no correlation between the number of EGF receptor on a cell surface and the mitogenic effect of EGF on the same tumor cells grown in semi-solid medium.

Biopsy↗
PubMed1981

Mechanism of synergistic induction of DNA synthesis by epidermal growth factor and tumor promoters.

Evidence is presented to support our previously proposed hypothesis that the hyperplastic effect of tumor promoters is related to their ability to alter existing physiological levels of growth factors in target tissues. Epidermal growth factor and phorbol ester tumor promoters acted synergistically at low (0.001-0.05 ng/ml) but not high (greater than 0.1 ng/ml) EGF concentrations to induce DNA synthesis in cultured Rat-1 fibroblast cells. The degree of synergism correlated with the tumor-promoting ability of the compound. The tumor promoters decreased 125I-EGF binding to cellular receptors in a dose-dependent manner that also correlated with the tumor-promoting ability of the compound. The inhibition of EGF binding by phorbol ester compounds resulted in a decrease in the amount of EGF degraded as compared to control cultures. At limiting EGF concentrations, the sparing of EGF degradation resulted in an increase in the amount of EGF remaining in the culture medium after 12 h of incubation and a concomitant increase in the amount of EGF bound to phorbol ester-treated cells at this time as compared to control cultures. The ability of a phorbol ester compound to alter EGF degradation and to stimulate DNA synthesis synergistically with EGF correlated with the tumor-promoting ability of the compound and occurred only a low EGF concentrations.

Animals↗
PubMed1981

Tumor promoter-induced inhibition of epidermal growth factor binding to cultured mouse primary epidermal cells.

The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and other diterpene derivatives on the binding of epidermal growth factor (EGF) to primary cultures of mouse epidermal cells was studied. 125I-EGF was used to study the specific binding of the growth factor to monolayer cultures of mouse epidermal cells grown under low-calcium culture conditions (0.06 mM Ca2+). Under these growth conditions, nonspecific binding did not exceed 10%. Initially, TPA decreased the binding of 125I-EGF to cells. However, when cells were incubated continuously in TPA plus EGF (0.25 ng/ml) for 19 hr, there was more EGF bound to the TPA-treated cells than to control cells. This phenomenon was not observed at high (5 ng/mg) EGF concentrations. Scatchard analysis of specific 125I-EGF binding at 4 degrees after a 1-hr pretreatment of the cells with TPA at 37 degrees converted a curvilinear plot to a linear plot. TPA induced a 25% decrease in the number of receptors per cell and eliminated binding of EGF to a class of high-affinity receptors. Preincubation of cells in TPA at 37 degrees for up to 13 hr followed by Scatchard analysis at 4 degrees showed that the curvilinear plot was restored and that the effects of TPA were partially reversible. TPA did not alter the rate at which bound EGF was degraded. However, at low EGF concentrations, TPA reduced the amount of EGF that was metabolized. The greater amount of EGF bound to TPA-treated cells over controls after long-term incubation was due to the presence of larger amounts of whole EGF in the media of TPA-treated cells at a time when the cells have regained their ability to bind EGF. A series of diterpene derivatives of different abilities to act as tumor promoters and hyperplasia-inducing agents were tested for their ability to influence EGF binding. The abilities of members of this series to decrease EGF binding and prevent degradation of EGF correlated more with their potentials to induce hyperplasia than with their tumor-promoting potentials. The ability of these diterpene derivatives to induced DNA synthesis with EGF synergistically may depend on the transient sparing of the EGF from degradation and subsequent binding of the spared EGF.

Animals↗
PubMedDate not supplied

Metalloproteinase-7 contributes to joint destruction in Staphylococcus aureus induced arthritis.

Septic arthritis induced by Staphylococcus aureus causes a rapid destruction of joint cartilage and periarticular bone. The mechanisms behind this phenomenon are not fully understood. Earlier studies have shown that cytokines and metalloproteinases are of importance in bone metabolism. Matrix metalloproteinase-7 (MMP-7) has pleiotropic function including facilitating migration of both macrophages and neutrophils. The aim of this study has been to investigate the significance of MMP-7 expression in septic arthritis. MMP-7 deficient mice and congeneic controls were intravenously inoculated with an arthritogenic dose of S. aureus LS-1. This study shows that MMP-7 deficient mice exposed to S. aureus developed significantly less severe arthritis both clinically and histologically. Despite this finding, bacterial growth in the deficient animals was significantly increased. In vitro responses to staphylococcal antigens and superantigens did not differ between MMP-7(+/+) and MMP-7(-/-) mice with respect to cytokine production and if anything increased the production of certain chemokines. In addition MMP-7(-/-) mice exhibited decreased numbers of peripheral blood mononuclear cells before and one day after bacterial inoculation, but increased numbers of peripheral granulocytes on day 1. In conclusion, MMP-7 contributes to the development of a destructive course of septic arthritis despite decreased bacterial load. In addition, expression of MMP-7 is of importance for the distribution of peripheral leukocytes.

Animals↗
PubMedDate not supplied

The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis.

BACKGROUND: The Fas ligand/Fas receptor (FasL/Fas) system is an important mediator of apoptosis in the immune system where the juxtaposition of cells expressing the cell-surface ligand induces the apoptotic pathway in Fas-expressing lymphocytes. The FasL/Fas system has also been shown to be involved in apoptosis in epithelial tissues, including the involuting rodent prostate. FasL can be shed through the action of an hitherto unidentified metalloproteinase to yield soluble FasL (sFasL), although the biological activity of sFasL has been disputed. RESULTS: Here we report that the matrix metalloproteinase matrilysin can process recombinant and cell-associated FasL to sFasL, and that matrilysin-generated sFasL was effective at inducing apoptosis in a target epithelial cell population. In the involuting mouse prostate, FasL and matrilysin colocalized to the cell surface in a restricted population of epithelial cells. Mice deficient in matrilysin demonstrated a 67% reduction in the apoptotic index in the involuting prostate compared with wild-type animals, implicating matrilysin in this FasL-mediated process. CONCLUSIONS: The results show that a functional form of sFasL was generated by the action of the metalloproteinase matrilysin, and suggest that matrilysin cleavage of FasL is an important mediator of epithelial cell apoptosis.

Animals↗
PubMedDate not supplied

Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis.

The matrix metalloproteinase matrilysin (MMP-7) has been demonstrated to contribute to tumor development. We have shown previously that members of the TNF family of apoptosis-inducing proteins are substrates for this enzyme, resulting in increased death pathway signaling. The goal of the current study was to reconcile the proapoptotic and tumor-promoting functions of matrilysin. In the human HBL100 and murine NMuMG cell lines that represent early stages of tumor progression and that express both Fas ligand and its receptor, exposure to matrilysin results in cell death that can be blocked by FasL neutralizing antibodies. Constitutive expression of matrilysin in these cell lines selects for cells with reduced sensitivity to Fas-mediated apoptosis as demonstrated both with a receptor-activating antibody and with in vitro activated splenocytes. Matrilysin-expressing cells are also significantly less sensitive to chemical inducers of apoptosis. We propose that the expression of matrilysin that has been reported at early stages in various tumor types can act to select cells with a significantly decreased chance of removal due to immune surveillance. As a result, these cells are more likely to acquire additional genetic modifications and develop further as tumors.

Animals↗
PubMedDate not supplied

Tumor and stromal expression of matrix metalloproteinases and their role in tumor progression.

The matrix metalloproteinases (MMPs) have been associated with tissue remodeling in many normal and pathological processes, and in particular are thought to be critical for tumor invasion and metastasis. MMP overexpression has been correlated with the stage of progression in several tumor types. Because of the aberrant nature of tumor cells, it has been assumed that the tumor cells themselves are responsible for this abnormal MMP production. However, recent in situ hybridization experiments have determined that, while some members of the MMP family are expressed within neoplastic cells, many are found in normal stromal components immediately adjacent to the tumor tissue. In this review, we address the potential roles of both tumor and stromal MMPs in tumor progression. Also, using MMP expression as a point of reference, we discuss some of the potential mechanisms involved in tumor/host interactions.

Animals↗