Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During human thymic differentiation, interactions between fibronectin (Fn)/beta1 integrins and hyaluronan (HA)/RHAMM control motility and Fn/beta1 integrins mediate spontaneous Fn-dependent adhesion. Multinegative (MN, CD3-4-8-) thymocytes exhibit strong spontaneous adherence to Fn (75%) that was efficiently inhibited by anti-alpha5beta1 and only weakly inhibited by anti-alpha4beta1. The relatively weak adherence of unfractionated thymocytes to Fn required both alpha4beta1 and alpha5beta1. Video time-lapse microscopy indicates that a subset of thymocytes also undergo spontaneous Fn-dependent motility mediated by alpha5beta1, alpha4beta1, and the HA-receptor RHAMM, but not by CD44. The loss of motility after hyaluronidase treatment of thymocytes indicated that motility is strongly dependent on HA. Of motile cells, 55% were DP, 19% were DN, and 24% were CD4+SP, but only 1% were CD8+SP. Overall, for MN thymocytes, beta1 integrin mediated Fn-adhesion, but after expression of CD4/CD8, beta1 integrins mediated Fn-dependent motility. Treatment with the activating anti-beta1 mAb QE.2E5 inhibited thymic motility and converted otherwise nonadherent thymocytes to an adherent state. High-avidity interactions via integrins appear to supercede the motogenicity of RHAMM and HA, suggesting that integrin avidity may regulate RHAMM. During thymic development, changes in adhesion or motility appear to be mediated by integrin avidity modulation.
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PMID:During human thymic development, beta 1 integrins regulate adhesion, motility, and the outcome of RHAMM/hyaluronan engagement. 985 Jan 61

Few animal models are available to study metastasis formation. The purpose of the present study was to obtain a useful model of metastasis formation in nude mice in an attempt to analyze the stroma reaction and in particular the production and the expression of hyaluronan (HA), hyaluronidase, and HA-binding sites by cultivated cells, and HA and hyaluronectin (HN) in the invasive areas of tumors. Nude mice were subjected to i.p. injections of several human cancer cell lines (PLC/PRF/5, HepG2, CB 191, CB 193, PC3, CAL 51, SA 87 and SA 98), and formation of metastases was analyzed in different organs (lung, liver, kidney, spleen and axillary nodes) by immunohistochemical techniques. CAL 51, a breast-cancer-metastasis-derived cell line with a normal karyotype, produced i.p. tumors in 75% animals and metastases in 90% animals (detected in the liver and axillary nodes). Two modes of invasion by CAL 51 cells were observed in the liver: one, direct, from the surface of the liver and the other, indirect, via the bloodstream. HA and HN were strongly expressed at the invasion areas. A cell line derived from hepatic metastasis of CAL 51 (HMD CAL 51) presented an abnormal karyotype. HMD CAL 51 produced more hyaluronidase (12-fold) and HA (10-fold) and expressed more CD44 (1.6-fold) and other HA-binding sites (9.5-fold) than the established cell line CAL 51. Our results show that i.p. injection of the CAL 51 cell line into nude mice provides a useful model of metastasis formation. The passage of the CAL 51 cells from the primary state to the metastatic state was characterized by a dramatic increase of HA and hyaluronidase production, and expression of HA, HN and HA-binding sites.
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PMID:Human breast-cancer metastasis formation in a nude-mouse model: studies of hyaluronidase, hyaluronan and hyaluronan-binding sites in metastatic cells. 1036 Aug 24

The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigated expression of the hyaluronic acid receptor CD44 protein in five human (T98G, A172, U87MG, 86HG39, 85HG66) and two rat (C6, 9L) glioma cell lines. Influence of anti-CD44 antibody and hyaluronidase-preincubation on the HA-binding was determined using HA/BSA (bovine serum albumin)-coated culture plates. While all gliomas were highly positive for CD44 with no differences in the number of positive staining cells, median fluorescence intensity decreased as follows: C6>T98G>9L>85HG66> 86HG39>A172>U87MG. Using HA/BSA coated culture plates the relative levels of specific adhesion to HA were determined as T98G>A172>9L>86HG39>U87MG> 85HG66. C6 cells failed to bind HA specifically. Incubation with anti-human-CD44 MAb significantly decreased HA-adhesion of T98G, A172, 85HG66 and U87MG human glioma cells. However the binding capacity was completely blocked only in 85HG66 cells. The three other cell lines kept a specific HA-adhesion after saturation of the receptor. Hyaluronidase pretreatment markedly enhanced HA-adhesion of C6 and 9L rat glioma cells. These results suggest that (i) HA-adhesion of malignant glioma cells is mainly, but not only, mediated by CD44, (ii) expression of CD44 does not correspond with adhesion capacity and (iii) cell-bound glycosaminoglycans may influence glioma cell adhesion to extracellular HA.
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PMID:CD44 expression and hyaluronic acid binding of malignant glioma cells. 1039 Jan 50

The glycosaminoglycan hyaluronate (HA) is part of the extracellular environment in bone marrow. We show here that HA activates signal transduction cascades important for hemopoiesis. In myeloid and lymphoid long-term bone marrow cultures (LTBMC), treatment with hyaluronidase (HA'ase) results in reduced production of both progenitor and mature cells. Exogeneous HA added to LTBMC had the opposite effect: it enhanced hematopoiesis. The effect of HA is mediated through two different HA receptors on bone marrow macrophage-like cells, one of which is CD44 while the other is unknown. HA induces bone marrow macrophages to secrete IL-1beta (CD44-dependent) and IL-6 (CD44-independent). The two receptors address different signal transduction pathways: CD44 links to a pathway activating p38 protein kinase while the other yet unknown receptor induces Erk activity. There was no difference of the effect of HA and HA'ase on hematopoiesis in LTBMC and on cytokine production by macrophages in CD44-deficient mice compared with wild-type mice, indicating that the CD44 hyaluronate receptor and its signal transduction can be compensated for. Our data suggest a regulatory role for the extracellular matrix component HA in hematopoiesis and show the induction of signal transduction by HA receptors.
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PMID:Hyaluronate-enhanced hematopoiesis: two different receptors trigger the release of interleukin-1beta and interleukin-6 from bone marrow macrophages. 1041 85

We investigated the mechanism of adhesion of highly malignant ascites hepatoma AH66F cells to mesothelial cells. The adhesion rate of AH66F cells to mesentery-derived mesothelial cells (M-cells) was about 46% at 37 degrees C, but it decreased to about 27% at 4 degrees C. The adhesion rate of AH66F cells was about 25% in the presence of leukocyte function-associated antigen 1 (LFA-1) mAb at both 4 C and 37 C. When M-cells were treated with hyaluronidase, the AH66F/M-cell adhesion was decreased to half at 37 degrees C and had nearly disappeared at 4 degrees C. The residual adhesion of AH66F cells to M-cells treated with hyaluronidase almost disappeared in the presence of LFA-1 mAb. AH66F cells strongly adhered to a hyaluronate (HA)-coated plate, but not to a bovine serum albumin-coated plate. AH66F cells expressed a CD44 molecule (a HA receptor) in the plasma membrane, with a molecular size of about 85 to 90 kDa, corresponding to the CD44H isoform. These results indicated that the adhesion of AH66F cells to mesothelial cells is composed of pathways of CD44/HA and LFA-1/ICAM-1.
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PMID:Adhesive interaction of highly malignant hepatoma AH66F cells with mesothelial cells. 1044 75

Adhesion and migration of mouse fetal liver (FL) cells to the thymus were investigated using cells from green fluorescent protein transgenic (GFP+) mice. FL cells from GFP+ embryos at 12 gestational days (E12) of mice were incubated with 2'-deoxyguanosine-treated fetal thymus lobe (from E14) by thymic repopulation (hanging drop) culture methods. GFP+ cells were observed in the thymus lobe at the end of the repopulation culture period. A large part of the infiltrated cells expressed CD44 until day 2 of culture on a permeable membrane, then lost the expression. CD25 expression was observed from day 1 to day 4. Around day 8, GFP+ cells became both CD4+ and CD8+. The results support the early observation of the sequential expression of CD44, CD25, and CD4/8 during the early stages of thymocyte development. When anti-CD44 mAb was added at the beginning of the repopulation culture period, GFP+ FL cells adhered to the surface of the thymus lobe but did not migrate into the thymus. Pretreatment of the thymus with hyaluronidase or hyaluronate produced results similar to the results of anti-CD44 treatment. On the other hand, the addition of anti-integrin alpha4 mAb inhibited adhesion to the thymus, and almost no GFP+ cells were seen on the surface of the thymus lobe. The data suggest that integrin alpha4 and CD44 play different roles, i.e., integrin alpha4 is required for the adhesion of FL cells to the thymus lobe and CD44 is required for the migration of the cells into the thymus.
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PMID:Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the fetal thymus. 1047 89

Malignant lymphocyte migration into and within lymphoreticular tissue is an important aspect of chronic lymphocytic leukemia (CLL), yet little is known about the processes involved. Our previous studies of integrin expression and function in CLL have shown that the abnormal cells are relatively nonadhesive and nonmotile on the protein ligands of these receptors. Here we show that CLL cells adhere to a non-protein ligand, hyaluronan (HA), and become motile (as assessed by both Boyden chamber migration and time-lapse video microscopy) on this ligand when stimulated with interleukin (IL) 8. The combined presence of HA and IL-8 was essential for this motility because IL-8 did not stimulate movement on other surfaces. Blocking antibodies showed that this motility is mediated by the receptor for HA-mediated motility (RHAMM), without the involvement of CD44. Moreover, confocal microscopy showed a polarized distribution of RHAMM and F-actin, but not CD44, in cells which had become motile on HA in the presence of IL-8. Immunohistochemical studies of nodes and spleen demonstrated an abundant reticular network of HA-containing fibers throughout diseased nodes and in splenic white pulp. The splenic red pulp and the luminal surface of high endothelial venules lacked HA. IL-8 was ubiquitously present in these tissues. CLL cells were shown to move spontaneously on fibroblast monolayers derived from lymphoid tissue; this movement was largely blocked by hyaluronidase or anti-RHAMM or anti-IL-8 antibodies. These studies indicate that IL-8-induced motility on HA is likely to be important for CLL cell migration through lymphoid tissue.
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PMID:The role of hyaluronan and interleukin 8 in the migration of chronic lymphocytic leukemia cells within lymphoreticular tissues. 1048 92

The regulation of hyaluronan synthesis and shedding was analysed in human fibroblasts and in two melanoma cells that differed in the metastatic potential and proteolysis of the hyaluronan receptor CD44. Dissociation of nascent hyaluronan from plasma membranes isolated from fibroblasts by high salt concentrations led to activation of hyaluronan synthase. Hyaluronan synthesis was also enhanced in plasma membranes from fibroblasts that had been treated with hyaluronidase or trypsin. Hyaluronan oligosaccharides stimulated hyaluronan production in fibroblast cultures. These results indicated that nascent high-molecular-mass hyaluronan inhibited its own chain elongation, if it was retained in the vicinity of the synthase by cell-surface receptors. The results also indicated that increased hyaluronan synthesis and shedding correlated with proteolysis of CD44 on the melanoma cell lines, which has been observed by others.
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PMID:Synthesis and shedding of hyaluronan from plasma membranes of human fibroblasts and metastatic and non-metastatic melanoma cells. 1049 13

We have observed that the spent culture media in suspended chondrocyte cultures is essential for the survival of the cells, since complete change of the spent media induces severe programmed cell death (apoptosis). Moreover, we showed that extracellular matrix (ECM) molecules in the culture media provide vital chondrocyte-matrix interactions; when media are changed, cells are deprived of matrix molecules and undergo apoptosis. In this paper we report that interaction with collagen, a ubiquitous extracellular matrix molecule, is essential for chondrocyte survival. Such an interaction causes chondrocyte aggregation and reduces the level of chondrocyte apoptosis. Hyaluronan, an abundant ECM molecule, can influence the effects of collagen by preventing chondrocyte aggregation. Degradation of hyaluronan with hyaluronidase results in chondrocyte aggregation, and this reduces the level of chondrocyte apoptosis. Experiments with an antibody to integrin beta1 suggest that the collagen-chondrocyte interactions are mediated through integrin beta1, and these interactions may protect chondrocytes from apoptosis. We hypothesize that hyaluronan binds aggrecan and link protein, forming stable ternary complexes, which interact with the chondrocyte surface, perhaps via CD44, and thus maintains a stable chondrocyte-matrix network.
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PMID:beta-Integrin-collagen interaction reduces chondrocyte apoptosis. 1051 81

Pathological changes in inflammatory bowel disease include an increase in intestinal mucosal mononuclear leukocytes and hyperplasia of the muscularis mucosae smooth muscle cells (M-SMCs). Because virus infections have correlated with disease flare, we tested the response of cultured M-SMCs to respiratory syncytial virus, measles virus, and the viral analogue, poly(I.C). Adhesion of U937 cells and peripheral blood mononuclear cells was used to measure the leukocyte-interactive potential of M-SMCs. Untreated M-SMCs, only minimally adhesive for leukocytes, bound U937 cells after treatment with respiratory syncytial virus or measles virus. Mononuclear leukocytes also bound to poly(I.C)-treated M-SMCs. Although both vascular cell adhesion molecule-1 mRNA and protein increased 3-4-fold in poly(I.C)-treated M-SMC cultures, U937 cell adhesion was not blocked by an anti-vascular cell adhesion molecule-1 monoclonal antibody. However, hyaluronidase digestion of poly(I.C)- or virus-treated M-SMCs dramatically reduced leukocyte adhesion ( approximately 75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a approximately 3-fold increase in surface-bound hyaluronan on poly(I.C)-treated M-SMCs compared with untreated controls. In addition, pretreatment of mononuclear cells with a blocking anti-CD44 antibody, greatly decreased adhesion to poly(I.C)-treated M-SMCs. Recognition of this virus-induced hyaluronan/CD44 mechanism of mesenchymal cell/leukocyte interaction introduces a new avenue in the research of gut inflammation.
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PMID:Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C). 1052 64


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