Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos.

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

doi:10.1083/jcb.109.5.2471

Cited by 272 publications

(144 citation statements)

References 46 publications

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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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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 PAI-1 antisense and sense probes were prepared from pBSKShPAI-1 (16). The PAI-2 antisense probe was prepared from pDB4707 (17 (18).…”

Section: Methodsmentioning

confidence: 99%

“…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%

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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“…Production of serine proteinases, such as urokinase-type plasminogen activator (u-PA) by trophoblastic cells correlates temporally with blastocyst invasion Strickland, Reich and Sherman, 1976;Sappino et al, 1989;Behrendtsen, Alexander and Werb, 1992) Strong STB positivity (arrows) for ST3 is observed. ST3 is also expressed by some spindle-shaped IT (arrowheads) that are derived from negative TCC, become detached and infiltrate the maternal decidua.…”

Section: Introductionmentioning

confidence: 99%

Expression of stromelysin-3 in the human placenta and placental bed

et al. 1997

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Human placentation is mediated by fetal trophoblastic cells which penetrate into the decidualized uterine endometrium. Trophoblast invasion requires the precisely regulated secretion of specific proteinases able to degrade the endometrial basement membranes and extracellular matrix. To document further the involvement of these proteinases during human placentation, we evaluated in vivo the expression of stromelysin-3, a member of the metalloproteinase family, during the first and third trimesters of pregnancy, by means of immunohistochemistry, in situ hybridization and Northern blot analysis. Human extravillous trophoblasts invading the maternal decidua produced stromelysin-3 during both, the first and third trimesters of pregnancy, but to a lesser extent during the latter. In floating villi, stromelysin-3 expression was restricted to the syncytiotrophoblasts that line intervillous vascular spaces. In conclusion, stromelysin-3 is expressed by differentiated, non-proliferative villous and extravillous trophoblastic cells in early and late placental beds and villi, and its pattern of expression evolves during pregnancy. Our observations suggest that stromelysin-3 could play a role in human placentation.

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Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos.

Cited by 272 publications

References 46 publications

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

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

Plasminogen activation in melanocytic neoplasia

Expression of stromelysin-3 in the human placenta and placental bed

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