The plasminogen activation system in tumor growth, invasion, and metastasis

Generation of the serine proteinase plasmin from the extracellular zymogen plasminogen can be catalyzed by either of two other serine proteinases, the urokinase- and tissue-type plasminogen activators (uPA and tPA). The plasminogen activation system also includes the serpins PAI-1 and PAI-2, and the uPA receptor (uPAR). Many findings, gathered over several decades, strongly suggest an important and causal role for uPA-catalyzed plasmin generation in cancer cell invasion through the extracellular matrix. Recent evidence suggests that the uPA system is also involved in cancer cell-directed tissue remodeling. Moreover, the system also supports cell migration and invasion by plasmin-independent mechanisms, including multiple interactions between uPA, uPAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors, and growth factors. These interactions seem to allow temporal and spatial reorganizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. The increased knowledge about the plasminogen activation system may allow utilization of its components as targets for anti-invasive therapy.     

Control of enzyme secretion by non-cholinergic, non-adrenergic nerves in guinea pig pancreas

Depolarization of pancreatic cells by exposure to high potassium solutions is associated with release of amylase. In the guinea pig, but not the mouse or cat, this Ca-dependent amylase secretion is resistant to atropine blockade, thus Scheele and Haymovits concluded that the enzyme secretion evoked by K depolarization does not involve release of transmitter from intrapancreatic nerves but is a consequence of Ca uptake into acinar cells mediated by the membrane depolarization. This hypothesis is inconsistent with current concepts of stimulus--secretion coupling in electrically non-excitable cells. The observation of Scheele and Haymovits could, however, also be explained by the release of a non-cholinergic, secretomotor transmitter as a consequence of the depolarization of intrapancreatic nerves. By adapting the technique of electrical field stimulation of isolated pancreatic segments to our studies of amylase secretion, we have now been able to demonstrate both cholinergic and non-cholinergic, non-adrenergic secretomotor nerves in the guinea pig pancreas. Excitation of the non-cholinergic nerves stimulates amylase secretion by a different intracellular coupling mechanism from that activated by cholinergic nerves or by peptides belonging to the cholecystokinin, gastrin or bombesin families.     

OXI1 kinase is necessary for oxidative burst-mediated signalling in Arabidopsis

Active oxygen species (AOS) generated in response to stimuli and during development can function as signalling molecules in eukaryotes, leading to specific downstream responses. In plants these include such diverse processes as coping with stress (for example pathogen attack, wounding and oxygen deprivation), abscisic-acid-induced guard-cell closure, and cellular development (for example root hair growth). Despite the importance of signalling via AOS in eukaryotes, little is known about the protein components operating downstream of AOS that mediate any of these processes. Here we show that expression of an Arabidopsis thaliana gene (OXI1) encoding a serine/threonine kinase is induced in response to a wide range of H2O2-generating stimuli. OXI1 kinase activity is itself also induced by H2O2 in vivo. OXI1 is required for full activation of the mitogen-activated protein kinases (MAPKs) MPK3 and MPK6 after treatment with AOS or elicitor and is necessary for at least two very different AOS-mediated processes: basal resistance to Peronospora parasitica infection, and root hair growth. Thus, OXI1 is an essential part of the signal transduction pathway linking oxidative burst signals to diverse downstream responses.     

Extracellular but not intracellular application of peptide hormones activates pancreatic acinar cells.

Peptide hormones, like neurotransmitters, are traditionally thought to activate cells by interacting with receptor sites accessible only from the extracellular space. However, there is no available evidence that establishes whether intracellular injections of peptide secretagogues can or cannot initiate cell activation. In view of recent demonstration that peptide hormones can penetrate the intracellular space in some tissues and the reports that intracellular injections of the neurotransmitter, dopamine, into acinar cells of cockroach salivary gland cause stimulation it seems of fundamental importance to test directly whether introduction of peptide secretagogues inside acinar cells of mammalian exocrine tissue can induce cell activation without first interacting with the outer surface of the external cell membrane. The data presented here show that injections of the secretagogue peptides caerulein and bombesinnonapeptide (bombesin-NP) into pancreatic acinar cells fail to evoke the characteristic potential and conductance changes that are observed following extracellular applications of these peptides.     

Are prostaglandins involved in early estrogen action

Summary Prostaglandin biosynthesis inhibition by indomethacin blocks estrogen-induced uterine hyperemia, but does not block estrogen-induced uterine eosinophilia and edema.Acknowledgments. Supported by grant B 012815 from the Servicio de Desarrollo Cientifico, Artistico y de Cooperacion Internacional from the University of Chile.     

The effect of pancreozymin and acetylcholine on the membrane potential of the pancreatic acinar cells

Zusammenfassung Acetylcholin und Pancreozymin induzieren beide eine Depolarisation der Azinuszellmembran in der Bauchspeicheldrüse. Nur die Wirkung von Acetylcholin wird von Atropin blockiert. Das Ruhepotential kann auch durch eine erhöhte Kaliumkonzentration im Extrazellularraum reduziert werden, diese Wirkung wird nicht von Atropin beeinflusst. Die Acetylcholin-induzierte Depolarisation ist nicht von extrazellularer Kalziumkonzentration abhängig, sondern ist wahrscheinlich eine notwendige Bedingung für den Sekretionsprozess.

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Supported by grants from The Carlsberg Foundation, The Wellcome Trust and I. and H. Weismann's legat. Present address: Inst. Med. Physiol. C, Univ. Copenhagen, Denmark.

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Cholecystokinin-Pancreozymin was kindly provided by GIH research unit, Chemistry Department, Karolinska Institutet, Stockholm.     

Iodine accumulation by the nephridia ofSipunculus (Sipuncula)

Résumé La détermination du contenu d'iode dans les différents organes des espèces du genreSipunculus (Sipuncula) a montré que les néphridies présentent la plus haute concentration de cette substance, ensuite vient l'intestin et la trompe. La forte accumulation d'iode dans les néphridies laisse supposer que ces organes sont responsables du métabolisme des iodoprotéines dans ce groupe d'Invertébrés.