Formation and activation of fibroblast spheroids depend on fibronectin-integrin interaction.

Clustering of fibroblasts into spheroids induces a massive proinflammatory, proteolytic and growth-factor response, named nemosis, which promotes tumor cell invasiveness and differentiation of leukemia cells. We have now sought to investigate mechanisms leading to the formation of multicellular spheroids and subsequent activation of fibroblasts (nemosis). Cell lines either lacking fibronectin expression (FN-/-) or expressing FN with a mutated integrin-binding site (FNRGE/RGE) were unable to form compact spheroids.

Cell-cell contact activation of fibroblasts increases the expression of matrix metalloproteinases.

Background: We recently found that direct homotypic cell-cell contacts between human dermal fibroblasts induce a novel form of cell activation leading to non-apoptotic programmed cell death. As the major features of this process we identified massive induction of cyclo-oxygenase-2 and production of inflammatory prostaglandins. On the surface of the decomposing spheroids, activation of the major extracellular proteolytic cascade, plasminogen activation, associated with surface exposure of alpha-enolase, took place.

High concentrations of plasminogen activator inhibitor-1 in lungs of preterm infants with respiratory distress syndrome.

Background: Among preterm infants, respiratory distress syndrome (RDS) is characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers inhibit surfactant function effectively. However, little is known about potential disturbances of intraalveolar fibrinolysis in RDS.

Plasminogen activators and their inhibitors in human saliva and salivary gland tissue.

The purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell-free saliva and to investigate their expression in salivary gland tissue. Saliva samples were obtained from 34 patients visiting a neurological out-patient department. The activities of tissue and urokinase plasminogen activators (tPA and uPA, respectively), the relative inhibition of tPA, and the amounts of plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2, respectively) in cell-free saliva were studied.

Plasminogen activators and their inhibitor gene expression in cutaneous NF1-related neurofibromas.

Cutaneous neurofibromatosis 1 (NF1)-related neurofibromas are benign tumors and composed of Schwann cells, perineurial cells and/or fibroblasts, endothelial cells, mast cells and macrophages. Extracellular proteolysis namely plasminogen activation (PA) operates in many tissue destructive processes. We wanted to study plasminogen activators, urokinase (uPA) and tissue type (tPA) and their inhibitor PAI-1, which have not earlier been studied comprehensively in cutaneous NF1-related tumors.