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)

Over the past several years, many tumor markers, including cell surface antigens, T-antigen, ras p55, and ras p52 proteins, have been studied as potential tumor markers of bladder cancer. The lack of specificity and inconsistency of these markers led us to develop a new method for studying the urinary excretion of autocrine motility factor (uAMF) and tumor cell collagenase stimulating factor (TCSF) in 24-hour and first morning voided specimens. AMF is a glycoprotein secreted by the malignant cells and is responsible for cell locomotion, a key event in invasion and metastases of the malignant cells. TCSF is a membrane bound glycoprotein of tumor cells that stimulates fibroblast collagenase production. We have utilized an enzyme-linked immunoabsorption assay to detect the levels of uAMF and TCSF in urine samples collected from normal volunteers, patients with benign diseases, and patients with bladder cancer. Our data indicate that urinary concentrations of uAMF and TCSF are elevated in patients with bladder cancer. Furthermore, the levels of uAMF and TCSF are more elevated in invasive tumors as compared with benign counterparts. We have localized uAMF and TCSF in bladder cancer cells, utilizing immunohistologic techniques.
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PMID:A new method for evaluation of urinary autocrine motility factor and tumor cell collagenase stimulating factor as markers for urinary tract cancers. 212 27

A family of dendritic cells has been identified in situ and in vitro by microscopy and immunolabeling. The members of this family include the dendritic cells isolated from lymphoid organs, Langerhans cells [LC] of the epidermis, veiled cells in afferent lymph, and interdigitating cells [IDC] in the T-cell areas. Some common features to all members of the family are high levels of MHC class II antigens, a lack of most B and T cell markers, and an absence or low levels of macrophage/granulocyte antigens. This review summarizes the markers of mouse dendritic cells as assessed by a panel of monoclonal antibodies, and stresses a few recent findings. 1) In spleen, there are two populations of dendritic cells. More than 75% of isolated cells are 33D1+, NLDC145-, and J11d-, while the remainder have the reciprocal phenotype and thus share the NLDC145 antigen of IDC. Thymic dendritic cells, released by collagenase digestion, and epidermal LC also are 33D1-, NLDC145+, J11d+. 2) When epidermal LC are placed in culture, there are changes in cell function and phenotype. There is a decrease in Fc gamma receptors and the F4/80 macrophage antigen, an increase in class I and II MHC products and p55 IL-2 receptors, and persistence of the NLDC145 IDC antigen. The cultured LC thereby resembles the IDC. 3) A new antibody N418 shows that dendritic cells express the p150/90 member of the leukocyte beta 2 integrin family. Immunolabeling of tissue sections of spleen indicates that N418+ dendritic cells not only are present in the periarterial sheaths, the location of IDC, but also in "nests" at the periphery of the T area where 33D1 has been found. The peripheral collections interrupt the marginal zone of macrophages that separates white and red pulp, and places the dendritic cells in the path of T cells as they move through the white pulp. Therefore the members of the dendritic cell family have important markers in common, as well as differences that are associated with state of immunologic function and location.
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PMID:The surface of dendritic cells in the mouse as studied with monoclonal antibodies. 215 4

The aim of this study was to examine the roles of the TNF receptors p55 and p75 in the TNF-enhanced expression of collagenase by human dermal fibroblasts. The agonistic p55 monoclonal antibody Htr9 and TNF induced production of similar amounts of collagenase. Polyclonal or monoclonal agonistic p75 antibodies failed to enhance collagenase production, and the antagonistic p75 antibody 5E12 did not inhibit TNF-enhanced expression of collagenase. This strongly suggests that p55, but not p75, is involved in TNF-induced production of collagenase. Cells continued to produce an elevated level of collagenase after the removal of TNF or Htr9. These data suggest that it may be useful to use specific inhibitors of collagenase rather than to block cytokine action directly in the treatment of diseases with chronic enhanced collagenolytic activity. A peptide of residues 36-62 of TNF previously reported to be chemotactic to leukocytes was also able to enhance the expression of collagenase activity by dermal fibroblasts. Thus, design of peptides with specific TNF effects may offer a novel approach for treatment of fibrotic disorders.
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PMID:Evidence for exclusive role of the p55 tumor necrosis factor (TNF) receptor in mediating the TNF-induced collagenase expression by human dermal fibroblasts. 882 62

TNF-alpha and lymphotoxin alpha (TNF-beta) are pleiotropic cytokines with regulatory functions in inflammatory reactions and T cell activation. Natural TNF inhibitors such as soluble TNF-binding proteins, i.e. TNFsR55 and TNFsR75, are shed from white blood cells and probably other cells. These naturally occurring inhibitors of TNF are shown to be 10 times less effective than the bivalent antagonist of TNF, recombinant soluble TNF receptor p55-human gamma 3 fusion protein (rsTNFR-p55h gamma 3), in controlling the release of prostaglandin E2 (PGE2) and collagenase by fibroblasts, as well as in controlling T cell proliferation. In order to block the action of rhTNF-alpha added to fibroblasts, a fivefold excess of rsTNFR-p55h gamma 3 was sufficient, but concentrations of a hundred to a thousand times higher were required to obtain a significant inhibition of T cell activation. This concentration appears to be required to block membrane-bound TNF-alpha on peripheral blood mononuclear cells as shown by Scatchard analysis. We additionally show that rsTNFR-p55h gamma 3 at high concentrations also blocks T cell activation by dendritic cells. In conclusion rsTNFR-p55h gamma 3 has a much higher anti-inflammatory effect than immunosuppressive effect.
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PMID:Production of prostaglandin E2 and collagenase is inhibited by the recombinant soluble tumour necrosis factor receptor p55-human gamma 3 fusion protein at concentrations a hundred-fold lower than those decreasing T cell activation. 901 Jun 78

Intrasplenic administration of a colon adenocarcinoma cell line, colon 26, induced tumor necrosis factor (TNF) alpha protein expression around the central and portal veins of the liver at 3 days, and liver metastases by 24 days after the tumor injection, in 90% of wild-type (WT) mice. To explore the roles of TNF-alpha in the process, we administered colon 26 cells into tumor necrosis factor receptor p55 (TNF-Rp55) knockout (KO) mice. Less than 50% of TNF-Rp55 KO mice developed liver metastasis with significantly lower liver weights and the volumes of metastatic foci. These observations suggest the critical roles of TNF-Rp55-mediated signals in this liver metastasis model. The intrasplenic tumor injection induced mRNA expressions of vascular endothelial growth factor, heparin-binding epidermal growth factor, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 at similar levels in the livers of both WT and TNF-Rp55 KO mice. Immunohistochemical analyses of the livers of WT mice after tumor injection demonstrated the enhanced expression of vascular cell adhesion molecule (VCAM)-1 and E-selectin on sinusoidal endothelial cells. Enhanced E-selectin expression was similarly observed in the liver of TNF-Rp55 KO mice after tumor injection. However, the enhancement in VCAM-1 mRNA expression and its protein production was significantly attenuated in the liver of TNF-Rp55 KO mice when compared with WT mice. Collectively, these observations suggest that TNF-Rp55-mediated signals can up-regulate both VCAM-1 expression in the liver and subsequent liver metastasis after intrasplenic tumor injection.
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PMID:Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells. 1243 67