Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD44-negative T lymphoma AKR1 (CD44.2 genotype) was transfected with a CD44.1 cDNA. The intact cDNA conferred on the transfected cells the ability to bind hyaluronic acid (HA) both from solution and immobilized on culture plates. It also conferred a CD44-dependent and hyaluronidase-sensitive increase in adhesion to a lymph node endothelial cell line. A mutant cDNA which codes for a CD44 molecule lacking most of the cytoplasmic domain of CD44 was also transfected into AKR1, and cell sorting was used to select transfectants expressing levels of cell surface CD44 expression comparable with the line transfected with the wild-type CD44 cDNA. The cells transfected with the mutant construct bound fluoresceinated HA from solution very poorly, but did adhere to immobilized HA, though less well than cells transfected with the wild-type construct. This result indicates that the cytoplasmic domain of CD44 is necessary for binding of HA from solution but is not required for binding to immobilized HA, although it may contribute to adhesion following ligand recognition. A monoclonal antibody (mAb), IRAWB 14, which reacts with CD44 on all CD44+ cells dramatically induced HA binding by some CD44+ cell lines that did not constitutively bind HA. The transfectant expressing a CD44 molecule with a truncated cytoplasmic domain could be induced by this antibody to bind fluoresceinated-HA from solution. Splenic T cells did not bind fluoresceinated HA constitutively. In the presence of the IRAWB 14 mAb, virtually all CD44+ splenic T cells bound HA. Induction was immediate and occurred equally well at room temperature and at 4 degrees C, indicating that the new HA-binding activity was due to preexistent CD44 molecules. These results are compatible with an antibody-induced activation of CD44 by either a conformational change in the CD44 molecule or a change in the distribution of CD44 molecules on the cell surface.
...
PMID:Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. 173 Sep 18

X-ray-induced, lymphoblastic, T-cell lymphoma/leukemias from irradiated RF mice were observed to uniformly expressed a 44-kd oncofetal antigen (OFA). The OFA polypeptide was detected by flow cytometry, affinity column SDS-PAGE analysis, and immunoblotting with monoclonal antibody (MAb) 115 prepared against syngeneic mouse fetus. X-ray and ultraviolet (UV) induced murine fibrosarcoma cell lines, used as classic models in radiation biology, were also found to express the OFA, which suggested that the 44-kd OFA was a general transformation marker of tumors. Adult mouse thymocytes and other adult tissues expressed no OFA. The 44-kd polypeptide was located at the surface membrane of the tumors examined. In contrast to other reports, lymphoblastic lymphoma cell lines expressed the OFA as a cross-protective, rather than an individually-specific, tumor-associated transplantation antigen. Pronase treatment removed OFA from the surface of living lymphoma cells, whereas collagenase, neuraminidase, and hyaluronidase did not. The OFA was rapidly reexpressed upon culture of the pronase-treated cells. Taken together, these results suggest that the 44-kd OFA polypeptide described here may provide a useful cell surface marker for future radiation carcinogenesis studies. MAb 115 is a promising reagent for detecting tumor-associated 44-kd OFA, for assessing immunoregulatory perturbations to the OFA caused by radiation damage and for investigating the immunopathology of OFA-associated radiation damage.
...
PMID:Radiation-induced lymphoblastic lymphomas/leukemias and sarcomas of mice express conserved, immunogenic 44-kilodalton oncofetal antigen. 333 9

Similar to activated T cells, LB T cell lymphoma expresses the CD44 cell surface Ag. In addition, the vast majority of LB cells also express the beta 2 (CD18) and alpha L (CD11a) chains of LFA-1 integrin. In view of the finding that anti-CD18 mAb blocked spleen, but not lymph node invasion by LB cells inoculated s.c. into BALB/c mice, we tested the ability of anti-CD44 mAb (IM 7.8.1) to block the infiltration of LB cells into the lymph nodes. We found that, as opposed to anti-CD18 mAb, anti-CD44 mAb, as well as its F(ab')2 or Fab fragment, prevented lymph node infiltration but had no effect on spleen invasion. This conclusion was based on histologic examination and [3H]thymidine incorporation into proliferating LB cells invading the lymphoid organs. Histologic analysis further demonstrated that LB cells invade the lymph node via the afferent lymphatics. The surface expression of CD44 molecules on LB cells was enhanced after PMA activation. PMA activation also enabled in vitro binding of the lymphoma to hyaluronic acid (HA), a known ligand of CD44. Because anti-CD44 mAb, its F(ab')2 or Fab fragment, and hyaluronidase blocked this binding, we also tested the ability of the enzyme to inhibit lymph node invasion by LB cells. We established through histologic examination and [3H]thymidine incorporation that hyaluronidase protected the lymph node, but not the spleen, from invasion by the lymphoma.
...
PMID:Lymph node (but not spleen) invasion by murine lymphoma is both CD44- and hyaluronate-dependent. 753 6

Little is known about how lymphocytes migrate within secondary lymphoid organs. Stromal cells and their associated reticular fibers form a network of fibers that radiate from high endothelial venules to all areas of the lymph node and may provide a scaffold for lymphocyte migration. We studied interactions of lymphocytes with cultured human tonsillar stromal cells and their extracellular matrix using shear stress to distinguish transient interactions from firm adhesion. Tonsillar lymphocytes and SKW3 T lymphoma cells tethered and rolled on monolayers of cultured tonsillar stromal cells and their matrix. A significant proportion of these rolling interactions were independent of divalent cations and were mediated by CD44 binding to hyaluronan, as shown by inhibition with mAb to CD44, soluble hyaluronan, as hyaluronidase treatment of the substrate, and O-glycoprotease treatment of the rolling cells. O-glycoprotease treatment of the substrate also blocked binding completely to stromal matrix and partially to stromal monolayers. SKW3 cells tethered and rolled on plastic-immobilized hyaluronan, confirming the specificity of this interaction. By contrast, monolayers of resting or stimulated human umbilical vein endothelial cells failed to support CD44- and hyaluronan-dependent rolling. SKW3 cells added under flow conditions to frozen sections of human tonsil bound and rolled along reticular fibers in the presence of EDTA. Rolling was blocked by either CD44 mAb or hyaluronan. We propose that lymphocytes migrating through secondary lymphoid organs may use CD44 to bind to hyaluronan immobilized on stromal cells and reticular fibers.
...
PMID:CD44 and hyaluronan-dependent rolling interactions of lymphocytes on tonsillar stroma. 876 28

Vinorelbine tartrate (Navelbine, Burroughs Wellcome Company, Research Triangle Park, NC, USA) is a semisynthetic vinca alkaloid approved in many countries for the first-line treatment of patients with advanced non-small-cell lung cancer. It is also used in the treatment of advanced breast and ovarian cancers and lymphoma. Like other vinca alkaloids, Navelbine can cause skin necrosis as a consequence of inadvertent extravasation in surrounding tissues during intravenous administration. In such cases, early treatment is strongly advocated. There is no documented case of vinorelbine extravasation in the literature. The authors herein report two cases successfully treated with hyaluronidase injections plus saline flushout under local anesthesia.
...
PMID:Two case reports of vinorelbine extravasation: management and review of the literature. 1140 Dec 8

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.
...
PMID:CD44-dependent lymphoma cell dissemination: a cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes. 1168 6

Interaction between hyaluronic acid (HA) and CD44 has been considered a key event in tumor invasion and metastasis. HA is a linear, high molecular weight glycosaminoglycan in its native state, but fragmented low molecular forms are found at sites ofneoplastic or inflammatory infiltrates. Both high and low molecular weights HA are involved in diverse biological functions. In this study, we used two clonal variants of a T cell murine lymphoma designated LBLa and LBLc. These cell lines were found to differ in their in vivo and in vitro growth rates. LBLa grew faster and exhibited an enhanced invasive capacity as compared to LBLc. In contrast, cell lines did not differ in the expression of surface markers (CD8, CD24, CD25, CD44, and CD18), or in their capacity to bind HA. However, LBLa cells exhibited higher capacity to migrate to low molecular weight HA than did LBLc. Migration was mediated by CD44 since it was abrogated by anti-CD44 monoclonal antibody as well as by hyaluronidase. We suggest that interaction between CD44 and low molecular weight HA may trigger migration mechanisms in LBLa cells, thus contributing to enhanced invasive cell capacity.
...
PMID:Interaction of CD44 with different forms of hyaluronic acid. Its role in adhesion and migration of tumor cells. 1252 Nov 33

CD44 on leukocytes binds to its glycosaminoglycan (GAG) ligand, hyaluronic acid, and mediates the rolling of leukocytes on vascular endothelial cells. We previously reported that the recombinant CD44 protein binds to other GAGs, including chondroitin sulfates (CS), although the physiological significance of this interaction has remained unclear. Here we report that the CD44 expressed on mouse lymphoma BW5147 cells supports cell binding to immobilized CS under static conditions and mediates cell rolling in CS-coated glass capillary tubes under shear stresses ranging from 0.5 to 1.5 dyn/cm(2), which is within the physiological range of forces in venules. Both interactions were completely inhibited by pretreating the cells with an anti-CD44 antibody or by pretreating the CS with chondroitinase ABC, but not hyaluronidase. To address the role of the CD44-CS interaction in vivo, we examined the tissue localization of the CS that interacts with CD44. Interestingly, a recombinant CD44 fusion protein bound to hepatic sinuosoidal endothelial cells where CS was also expressed, as assessed by immunohistochemistry. These findings support the involvement of the CD44-CS interaction in the primary adhesion of lymphocytes to endothelial cells and raise the possibility that this interaction plays a role in the capture of CD44-positive cells, such as activated T cells and certain tumor cells, by the hepatic sinusoidal vasculature.
...
PMID:CD44-chondroitin sulfate interactions mediate leukocyte rolling under physiological flow conditions. 1515 13

Hyaluronidases and their substrate, hyaluronan (HA), were mainly explored in solid tumors but rarely in hematologic malignancies. While HA involvement was demonstrated in invasion and metastasis in most cases of solid tumors, the role of hyaluronidases in cancer progression remains controversial. One of the hyaluronidases, HYAL2, is suspected to be involved in the first step of HA degradation. In this work, HYAL2 mRNA, HA and total hyaluronidases expression were examined in lymphoma tissue extracts and correlated to the lymphoma subtype. Real-time RT-PCR was performed to evaluate HYAL2 mRNA. HA and hyaluronidase were assayed by enzyme-linked sorbent assay. Our results showed that HYAL2 mRNA expression was correlated to lymphoma diagnosis (p = 6 x 10(-3)) and was significantly lower in high-grade lymphoma, i.e., diffuse large B-cell diffuse lymphomas (DLBCLs). Several forms of hyaluronidase were detected by zymography and total hyaluronidase activity detected in tissue extracts was not significantly different according to tumor grade. HA levels also correlated to lymphoma subtype (p = 1 x 10(-5)) and were higher in DLBCLs. Moreover, HYAL2 mRNA and HA expressions were inversely correlated (p = 0.035). HYAL2 gene is localized on chromosome 3p21, which contains candidates tumor suppressor genes. Our results suggest that HYAL2 may have a prognostic significance in lymphomas and an antioncogenic activity. Conversely, HA overexpression in high-grade lymphomas is in favor of its involvement in tumor development and could provide a useful target for lymphoma therapy using HA-binding peptides.
...
PMID:Expression of HYAL2 mRNA, hyaluronan and hyaluronidase in B-cell non-Hodgkin lymphoma: relationship with tumor aggressiveness. 1709 31

OHK cells, a human lymphoma cell line, are known to produce large amounts of hyaluronan. We investigated the effect of 4-methylumbelliferone, an inhibitor of hyaluronan synthesis, on the activity of matrix metalloproteinases in OHK cells. Matrix metalloproteinase-9 was detected on gelatin zymography as the main metalloproteinase excreted into the medium of cultured OHK cells, and 4-methylumbelliferone added to the medium decreased the activity of the enzyme in a dose-dependent manner. Addition of Streptomyces hyaluronidase to the medium during cultivation did not decrease the enzyme activity. Reverse transcription-polymerase chain reaction revealed that 4-methylumbelliferone markedly decreased the level of mRNA for matrix metalloproteinase-9 in cultured OHK cells. A similar decrease of the activity of matrix metalloproteinase-9 by 4-methylumbelliferone was also observed in cultured human breast and colon carcinoma cells. These results suggest that 4-methylumbelliferone suppresses the expression of matrix metalloproteinase-9 in cultured cancer cells.
...
PMID:Suppression of matrix metalloproteinase-9 by 4-methylumbelliferone. 1747 Apr 3


1 2 Next >>

---