Sites of synthesis of urokinase and tissue-type plasminogen activators in the murine kidney.

Sappino, André‐Pascal; Huarte, Joaquín; Vassalli, Jean‐Dominique; Belin, Dominique

doi:10.1172/jci115104

Cited by 153 publications

(104 citation statements)

References 54 publications

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“…The blots were hybridized at 58°C, and the three stringency washes were done at 760C. RNase protection assays and in situ hybridizations were performed as described by Belin et al (1989) and Sappino et al (1991). A 1 kbp murine PN-I probe, obtained by PCR amplification of seminal vesicle cDNA using two oligonucleotides corresponding to regions conserved between rat and human PN-I (Sommer et al, 1987), was cloned into pGEM-3Z and transcribed with SP6 RNA polymerase; the probe corresponds to the sequence coding for 11e42 to Ser366 (Sommer et al, 1987).…”

Section: Resultsmentioning

confidence: 99%

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

et al. 1993

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A search for inhibitors of urokinase-type plasminogen activator (uPA) in the male and female murine genital tracts revealed high levels of a uPA ligand in the seminal vesicle. This ligand is functionally, biochemically and immunologically indistinguishable from protease-nexin I (PN-I), a serpin ligand of thrombin and uPA previously detected only in mesenchymal cells and astrocytes. A survey of murine tissues indicates that PN-I mRNA is most abundant in seminal vesicles, where it represents 0.2-0.4% of the mRNAs. PN-I is synthesized in the epithelium of the seminal vesicle, as determined by in situ hybridization, and is secreted in the lumen of the gland. PN-I levels are much lower in immature animals, and strongly decreased upon castration. Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control.

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Section: Resultsmentioning

confidence: 99%

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

et al. 1993

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“…Also in man, PAI-1 deficiency is without clinical manifestations, except for mild bleeding disorders (Fay et al, 1997). Nevertheless, plasminogen activation is thought to play a role in processes like implantation (Sappino et al, 1989;Hofmann et al, 1994;Feng et al, 2001), embryogenesis (Sappino et al, 1991;Ha¨ckel et al, 1995) and angiogenesis (Pepper, 2001), and PAI-1 is expressed during these processes (Hofmann et al, 1994;Ha¨ckel et al, 1995;Pepper et al, 1996;Feng et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice

et al. 2003

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The plasminogen activator inhibitor-1 (PAI-1) blocks the activation of plasmin(ogen), an extracellular protease vital to cancer invasion. PAI-1 is like the corresponding plasminogen activator uPA (urokinase-type plasminogen activator) consistently expressed in human breast cancer. Paradoxically, high levels of PAI-1 as well as uPA are equally associated with poor prognosis in cancer patients. PAI-1 is thought to play a vital role for the controlled extracellular proteolysis during tumor neovascularization. We have studied the effect of PAI-1 deficiency in a transgenic mouse model of metastasizing breast cancer. In these tumors, the expression pattern of uPA and PAI-1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis. In a cohort of 63 transgenic mice that were either PAI-1-deficient or wild-type sibling controls, primary tumor growth and vascular density were unaffected by PAI-1 status. PAI-1 deficiency also did not significantly affect the lung metastatic burden. These results agree with the virtual lack of spontaneous phenotype in PAI-1-deficient mice and humans and may reflect that the plasminogen activation reaction is not rate limiting for tumor vascularization and metastasis, or that there is a functional redundancy between PAI-1 and other inhibitors of the uPA/plasmin system, masking the effect of PAI-1 deficiency.

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“…In situ hybridizations were carried out on 5-fim cryostat tissue sections as described previously (8,18,19). Localizations of mRNAs were performed by hybridization of 32P, 33P, or 'H-labeled cRNA probes to tissues sections and revealed either by film autoradiography for macroscopic localization or by emulsion autoradiography for microscopic localization.…”

Section: Methodsmentioning

confidence: 99%

“…Histological zymographies were performed on 10-/Â¿m cryostat tissue sections as described elsewhere (19). Sections were overlaid with a mixture containing 0.75 ml of phosphate-buffered saline (with 0.9 mM UROKJNASE IN MELANOMAS Ca2+ and 1 HIM Mg2 +), 2% nonfat dry milk, 0.9% agar, and 40 ng/ml of purified human plasminogen in PBS.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Plasminogen activation in melanocytic neoplasia

et al. 1993

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A large body of experimental evidence suggests that plasminogen acti vators provide tumoral cells with efficient means to degrade extracellular matrix constituents and thereby facilitate their dissemination to distant sites. Melanocytic neoplasia encompass a spectrum of lesions exhibiting diverse clinical behavior that remain difficult to predict with current histopathological evaluations. Little information concerning the contribu tion of plasminogen activation in diagnostic specimens of human melanocytic tumors is presently available. We thus analyzed biopsy specimens of pigmented skin lesions by histolÃ³gica! techniques that identify the cellular sites of synthesis of plasminogen activators and of their inhibitors and that localize the sites of plasminogen activators-catalyzed enzymatic activities. We found that urokinase-type plasminogen activators (uPA) and plasmin ogen activator inhibitor type 1 mRNAs accumulate in atypical nevocytes and in melanoma cells, but not in benign nevocytes. However, uPAcatalyzed proteolytic activity was detected exclusively in melanomas.These observations suggest that up-regulation of the uPA gene is an early feature of melanocyte transformation and that unbalanced enzyme/ inhibitor activity is associated with the malignant phenotype. By support ing a role for uPA in melanoma invasiveness, they provide a novel tool for the evaluation of atypia in nevi.

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Sites of synthesis of urokinase and tissue-type plasminogen activators in the murine kidney.

Cited by 153 publications

References 54 publications

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice

Plasminogen activation in melanocytic neoplasia

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