Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant class 2 plasminogen activator inhibitor (PAI-2) was used in an approach to probe the formation and location of enzymatically active urokinase-type plasminogen activator (u-PA) sites on the surface of cultured human rhabdomyosarcoma cells (RD cells). Activation of pro-u-PA on the cell surface and consequent binding of PAI-2 was dependent on the addition of native plasminogen to serum cultures of the cells. Inhibition of the enzyme activity of surface-bound u-PA by the added PAI-2 resulted in a 79% reduction in the capacity of the RD cells to generate cell surface-associated plasmin activity from bound plasminogen. Under these conditions, the PAI-2 probe was localized at focal adhesions of RD cells, where it colocalized with both extracellular u-PA and intracellular vinculin antigens in double immunofluorescence labeling. Specificity of the probe's interaction with cell surface-bound u-PA was confirmed by blocking with a monoclonal antibody to human u-PA, which could also inhibit the formation of bound plasmin activity. These results showed the assembly of the plasmin-generating system at focal adhesions and the accessibility of bound u-PA on which it depends to added PAI-2. Therefore, PAI-2 has the potential both to localize at sites of tumor expression of functionally active u-PA and simultaneously to inhibit cell surface plasminogen activation.
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PMID:Prourokinase activation on the surface of human rhabdomyosarcoma cells: localization and inactivation of newly formed urokinase-type plasminogen activator by recombinant class 2 plasminogen activator inhibitor. 213 29

Pro-urokinase (pro-uPA) and activated uPA are confined to focal adhesions and cell-cell contacts. We studied the distribution of the uPA receptor (uPAR) on human fibroblasts (HES) and rhabdomyosarcoma (RD) cells by immunofluorescence and immunoelectron microscopy. Two monoclonal antibodies (MAb) utilized were against uPAR: MAb R4, which reacts with occupied and unoccupied uPAR, was concentrated at focal adhesions; MAb R3 reacting with unoccupied receptor stained cell surfaces diffusely. MAb R4 stained cell-cell contacts, tips of microspikes, and co-localized with vinculin. Of the matrix and integrin components tested, alpha v beta 3 integrin was found at focal adhesions but more centrally than uPAR. Since uPAR is anchored to the plasma membrane through a GPI lipid, we studied its mobility by antibody-induced clustering. This revealed that unoccupied uPAR was relatively mobile; MAb R3 redistributed it to clusters. In contrast, uPAR R4 and uPA antibodies at the focal contact sites remained mostly within focal contacts. Addition of exogenous uPA resulted in loss of R3 staining and increase of uPA in focal adhesions. These results suggest that occupancy of the receptor with uPA is associated with localization to cell contact sites and restricted lateral mobility.
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PMID:Distribution and lateral mobility of the urokinase-receptor complex at the cell surface. 839 52

The microfilament-associated protein vinculin is a major constituent of muscle tissue localized in costameres and Z-discs of the sarcomeric apparatus, where it is thought to play a pivotal role in the alignment of sarcomeric myofibrils and the transduction of mechanical force between the internal contractile machinery and the extracellular environment. In order to investigate whether anti-vinculin antibodies are helpful in confirming the commitment of rhabdomyosarcomas to the myogenic pathway, we studied immunohistochemically the expression pattern of vinculin in a series of 7 human rhabdomyosarcomas including those of embryonal, botryoid, and pleomorphic subtypes. Using monoclonal antibody from clone hVIN-1 by APAAP techniques on formalin-fixed, paraffin-embedded tissue, all but one tumor, which was a primitive embryonal rhabdomyosarcoma, demonstrated a significant positive vinculin staining. Vinculin expression was most prominent in differentiated tumors with a focal staining pattern showing a high degree of correlation with rhabdomyoblasts, whereas a diffuse staining was observed in areas in which small, poorly differentiated tumor cells alone were present. Since vinculin immunoreactivity could also be demonstrated in cases of leiomyosarcoma, the positive immunohistochemical detection of vinculin was not exclusively restricted to mesenchymal tumors derived from sarcomeric muscle tissue. Immunodetectable amounts of nebulin could be revealed only in two embryonal rhabdomyosarcomas. Our results suggested that the positive identification of rhabdomyosarcoma achieved by using antibodies against vinculin in addition to other known myogenic markers may be particularly useful in the differential diagnosis of anaplastic, poorly differentiated sarcomas.
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PMID:Immunohistochemical detection of vinculin in human rhabdomyosarcomas. 906 83