Disease relevance of Adamts1

• Targeted inactivation of the ADAMTS1 gene results in morphological defects in the kidney, adrenal gland, and adipose tissue in addition to growth retardation and infertility in females [1].
• Here, we examined the effects of ADAMTS-1 overexpression on in vivo tumor growth and tumor metastasis [2].
• Neonatal calyceal dilation and renal fibrosis resulting from loss of Adamts-1 in mouse kidney is due to a developmental dysgenesis [3].
• Using a neutralizing monoclonal antibody specific for murine IFN gamma we show that endogenously produced IFN gamma plays an obligate role in mediating LPS-induced rejection of the Meth A fibrosarcoma tumor in syngeneic BALB/c mice [4].
• Expression of the serologically defined Meth A sarcoma antigen is not suppressed in hybrid cells containing a complete foreign (Chinese hamster) genome [5].

Psychiatry related information on Adamts1

• In spontaneous activity studies, doses of BNMPA ranging from 1 mg/kg to 50mg/kg failed to alter locomotor activity significantly from controls though 5 mg/kg METH alone significantly increased spontaneous activity [6].

High impact information on Adamts1

• Vaccination of mice with heat shock protein 70 (hsp70) preparations derived from the Meth A sarcoma, but not from normal tissues, renders the mice immune to a substantial challenge with Meth A sarcoma [7].
• In this report, we demonstrate that infusion of low concentrations of TNF (3 micrograms/animal) into mice bearing meth A fibrosarcomas leads to localized fibrin deposition with formation of occlusive intravascular thrombi in close association with the endothelial cell surface [8].
• The results of this study show that during growth of the immunogenic Meth A fibrosarcoma, two different types of suppressor T lymphocytes are generated in sequence [9].
• These results show that failure of intravenously-infused, tumor-sensitized T cells to cause regression of the Meth A fibrosarcoma growing in its syngeneic or semi-syngeneic host is caused by the presence of a tumor-induced population of cyclophosphamide-sensitive suppressor T cells [10].
• Chromosome and serologic analysis of microcell hybrids between Meth A sarcoma cells and Chinese hamster cells shows a clear correlation of Meth A antigen expression with the presence of the distal region of chromosome 12 (bands F1 and F2) [5].

Chemical compound and disease context of Adamts1

• Tumor necrosis factor/cachectin-induced intravascular fibrin formation in meth A fibrosarcomas [8].
• The combination of BLM or FUra with decaprenoic acid, when administered by iv injection to mice with fibrosarcoma Meth A (solid tumor system), did not produce synergism [11].
• Similar results were obtained when BALB/c mice were inoculated sc with a syngeneic BALB/c Meth A fibrosarcoma and treated with RP (5,000 IU/kg/day) and FUra (20 mg/kg/every 3d day) [12].
• The growth of Meth 1 fibrosarcoma (Meth 1), another syngeneic tumor of BALB/c origin, as a rechallenge tumor was unaffected by treatment with beta-carotene, thereby suggesting that beta-carotene may augment tumor rejection specific to tumor-specific antigens [13].
• Isolated membrane and cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A and CMS5, have TRA activity, and biochemical characterization of the active components from the cytosol and plasma membranes of these two tumors identified a glycoprotein of Mr 96,000 [14].

Biological context of Adamts1

• The ADAM-TS genes are dispersed in human and mouse genomes [15].
• Activation of the ADAMTS-1 promoter by PRA involves functional CAAT enhancer binding protein beta, nuclear factor 1-like factor, and three Sp1/Sp3 binding sites as demonstrated by transfection of mutated promoter constructs [16].
• Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases [17].
• The distribution of ADAMTS1 in the normal and wounded epidermis, its regulation in cultured keratinocytes, as well as the skin phenotype of ADAMTS1 knock-out mice suggests a role of this metalloproteinase in keratinocyte differentiation [18].
• Here we have shown up-regulation of ADAMTS1 expression in wounds of normal and particularly of healing-impaired genetically diabetic mice [18].

Anatomical context of Adamts1

• To analyze the molecular mechanisms by which LH and PR regulate this gene, truncations and site-specific mutants of ADAMTS-1 promoter-luciferase reporter constructs (ADAMTS-1-Luc) were generated and transfected into rat granulosa cell cultures [16].
• ADAMTS1 proteinase is up-regulated in wounded skin and regulates migration of fibroblasts and endothelial cells [18].
• Immunofluorescence staining identified macrophages as the source of ADAMTS1 in early wounds, whereas keratinocytes and fibroblasts produce this protein at later stages of wound healing [18].
• These data demonstrate that impairment of ovarian function to ovulate oocytes in ADAMTS-1 null mice occurs at two different levels: in the development of growing follicles and ovulatory processes [19].
• Furthermore, ADAMTS-1 null ovaries included a number of unusual atretic follicles that showed no sign of oocyte degeneration but lost the surrounding granulosa cell layers and were considered to be derived from type 4 or 5a follicles [19].

Associations of Adamts1 with chemical compounds

• Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor [16].
• Forskolin plus phorbol myristate acetate also increased promoter activity and, when added to cells cotransfected with PRA, ADAMTS-1 promoter activity increased further [16].
• ADAMTS-5, but not ADAMTS-1, -4, or -9, was up-regulated 8-fold by retinoic acid and 17-fold by IL-1alpha treatment [20].
• The growth of Meth 1, another syngeneic tumor of BALB/c origin, inoculated on day 10 as a rechallenge tumor was unaffected by the treatment with RP and/or FUra [12].
• Winn assay revealed that the suppressive effect on tumor growth of immune lymph node cells obtained from Meth A-inoculated beta-carotene-treated mice on day 12 was enhanced dose dependently [13].

Enzymatic interactions of Adamts1

• The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL) [21].

Other interactions of Adamts1

• BACKGROUND: A disintegrin and metalloproteinase with thrombospondin motifs 1, Adamts-1, is important for the development and function of the kidney [3].
• Immunohistochemical analysis demonstrated TGF-beta protein localized to infiltrating macrophages and glomeruli of Adamts-1 null mice [3].
• Furthermore, we provide evidence for a novel dual function of ADAMTS1 in fibroblast migration; although low concentrations of this protein stimulate fibroblast migration via its proteolytic activity, high concentrations inhibit this process because of binding to fibroblast growth factor-2 and subsequent inhibition of its promotogenic activity [18].
• No uterine phenotype was apparent in Adamts-1 null animals [22].
• Using in situ hybridization, we have localized ADAMTS1 transcripts predominantly to the epithelium of the developing lung, pancreas, kidney and to a subset of neurons in a temporally restricted manner [1].

Analytical, diagnostic and therapeutic context of Adamts1

• Immunohistochemistry was used to assess the localization of type IV collagen, TGF-beta and F4/80-positive macrophages in the kidneys of Adamts-1 null mice compared to wild-type control animals [3].
• Because the presence of suppressor T cells generated in response to the Meth A did not suppress the capacity of Meth A-bearing mice to generate and express immunity against a tumor allograft, it is obvious that they were not in a state of generalized immunosuppression [23].
• The results of this paper are consistent with the hypothesis that progressive growth of the Meth A fibrosarcoma evokes the generation of a T-cell-mediated mechanism of immunosuppression that prevents this highly immunogenic tumor from being rejected by its immunocompetent host [23].
• On the basis of preceding studies showing that tumor-induced, T cell-mediated immunosuppression serves as an obstacle to adoptive immunotherapy of the Meth A fibrosarcoma, it was predicted that cyclophosphamide treatment of tumor bearers would remove this obstacle and allow passively transferred immune T cells to cause tumor regression [10].
• It was shown that it is possible to cause the regression of large, established Meth A tumors by intravenous infusion of tumor-sensitized T cells from immune donors, but only if the tumors are growing in T-cell-deficient recipients [23].

References