Growth factor-like effect of urokinase type plasminogen activator in human renal cells

He, Cijiang; Rebibou, Jean-Michel; Péraldi, Marie-Noëlle; Meulders, Q.; Rondeau, Éric

doi:10.1016/0006-291x(91)90443-b

Cited by 41 publications

(21 citation statements)

References 13 publications

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“…Furthermore, we could not find any association between nuclear uPAR immunostaining and clinical or histopathological characteristics of the patients. It is not obvious why uPAR is accumulated in the nuclei of the pancreatic cancer cells, but it might be possible that uPAR influences gene transcription, as it has been previously suggested for some growth factors and also for uPA (He et al, 1991). Similar nuclear uPAR immunostaining has also been observed in some breast cancer samples, however the significance of this observation in breast cancer was also not obvious (Carriero et al, 1994).…”

Section: Discussionmentioning

confidence: 89%

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Cantero

Frieß²,

Deflorin³

et al. 1997

Br J Cancer

186

126

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Summary Urokinase plasminogen activator (uPA) is a serine proteinase that has been suggested to play an important role in cancer invasion and metastasis. It binds to a specific membrane receptor denominated uPA receptor (uPAR Pancreatic cancer has one of the poorest prognoses of all gastrointestinal malignancies, being the fourth or fifth leading cause of cancer-related deaths in Western industrialized countries (Bomman et al, 1994). Gudjonsson (1987), in his classical review of 37 000 patients with pancreatic cancer, demonstrated an overall survival rate of 0.4% and a median survival time of 5 months after the diagnosis was established. Once pancreatic cancer is clinically evident, it progresses at a rapid rate, and metastasis has usually occurred at the time of diagnosis. Consequently, many patients are not resectable at presentation, and the overall resection rate is often less than 30% (Gudjonsson 1987;Bomman et al, 1994). The mechanisms that regulate this aggressive growth behaviour in pancreatic cancer are not at all clear. Recently, it has been shown in pancreatic cancer that the concomitant overexpression of the epidermal growth factor (EGF) receptor and its ligands EGF-, TGF-alpha (Korc et al, 1992;Yamanaka et al, 1993a) and/or amphiregulin (Ebert et al, 1994a; Yokoyama et al., 1995a) is associated with shorter post-operative survival following tumour resection. In addition, enhanced expression of c-erbB-3 (Friess et al, 1995), TGF-fs and basic fibroblast growth

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Section: Discussionmentioning

confidence: 89%

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Cantero

Frieß²,

Deflorin³

et al. 1997

Br J Cancer

186

126

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“…For example, the proteolytically inactive uPA derivatives have been shown to initiate proliferation in osteoblast-like cells [33], whereas in renal cells [31] and fibroblasts [12, 32], the presence of both growth factor-like and proteolytic domains of uPA were required for mitogenesis. Our previous studies showed that uPA-mediated plasmin proteolysis is an important contributor to SMC proliferationin vitro [11] as well as in vivo [14, 15] after arterial injury.…”

Section: Discussionmentioning

confidence: 99%

“…uPA is now considered to be implicated in the regulation of cell proliferation and migration by means of its proteolytic as well as nonproteolytic properties [11, 12, 18,31,32,33]. For example, the proteolytically inactive uPA derivatives have been shown to initiate proliferation in osteoblast-like cells [33], whereas in renal cells [31] and fibroblasts [12, 32], the presence of both growth factor-like and proteolytic domains of uPA were required for mitogenesis.…”

Section: Discussionmentioning

confidence: 99%

Urokinase Plasminogen Activator in Injured Adventitia Increases the Number of Myofibroblasts and Augments Early Proliferation

Плеханова

Stepanova²,

Ratner³

et al. 2006

J Vasc Res

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Myofibroblasts are involved in vessel remodeling during the development of hypertension as well as after angioplasty and aortocoronary grafting, but the mechanisms of myofibroblastic phenotypic modulation are not fully elucidated. We assessed the role of urokinase plasminogen activator (uPA) and its proteolytic activity in myofibroblast differentiation and the early proliferation following mechanical injury of the rat carotid adventitia. The effects of perivascular application of recombinant uPA (r-uPA), proteolytically inactive r-uPA(H/Q) and uPA neutralizing antibody were evaluated 4 days after surgical injury to the adventitia. The phenotype of adventitial cells was assessed using anti-α-smooth muscle actin (α-SM actin) antibody, anti-SM heavy chain myosin, anti-high-molecular-weight caldesmon, anti-smoothelin and anti-ED-1 antibodies, proliferation by the expression of proliferating cell nuclear antigen, and the size of the adventitia by quantitative morphometry. Four days after injury, the intensive immunostaining for urokinase appeared in the rat carotid artery adventitia. At the same time, the frequency of α-SM actin-positive adventitial cells was 1.8 ± 1.1% in uninjured arteries and 25.2 ± 5.4% in injured arteries (p < 0.05), and the respective frequency of ED-1-positive cells 1.5 ± 1.1 and 25.0 ± 5.2%. The application of exogenous r-uPA doubled the numbers of α-SM actin-positive adventitial cells to 55.7 ± 6.8% (p < 0.05). ED-1-positive cells and proliferating cell nuclear antigen-positive cells as well as the size of the adventitia were also significantly increased after r-uPA compared with injury alone. In contrast, the proteolytically inactive r-uPA(H/Q) did not affect any parameters. The application of uPA neutralizing antibody attenuated the frequency of α-SM actin-positive cells to 12.6 ± 3.5% (p < 0.05), the frequency of ED-1-positive cells, and the numbers of adventitial cells. r-uPA stimulation of cultured human skin fibroblasts significantly increased the α-SM actin content in a concentration-dependent manner. In contrast, r-uPA(H/Q) did not induce changes in α-SM actin content. We conclude that uPA, which is upregulated in the injured adventitia, can augment adventitial cell accumulation, including myofibroblasts, and adventitia growth early after injury of the rat carotid artery adventitia by mechanisms involving proteolysis.

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“…A mitogenic effect of uPA has been demonstra in vitro in different cell lines, both normal and neoplastic (Rabbai et al, 1990;He et aL 1991;De Petro et al, 1994;luperello et al, 1996).…”

Section: Effect Of E2 On the Pas Wctty In Bc-2 Cellsmentioning

confidence: 99%

Oestradiol regulation of the components of the plasminogen-plasmin system in MDA-MB-231 human breast cancer cells stably expressing the oestrogen receptor

Levenson

Kwaan²,

Svoboda³

et al. 1998

Br J Cancer

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Summary To understand the hormonal regulation of the components of the plasminogen-plasmin system in human breast cancer, we examined the oestradiol (E2) regulaton of plasminogen activators (PAs), namely urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and uPA receptor (uPAR), in our model system. We used stable transfectants of the MDA-MB-231 human breast cancer cells that express either the wiki-type (S30 cells) or the mutant 351a ,! oestrogen receptor (ER) (BC-2 cells). Northem blot analysis showed that there was a concentration-dependent down-regulation of uPA, tPA and PAI-1 mRNAs by E2. In contrast, uPAR mRNA was not modulated by E2. The pure anti-oestrogen ICI 182,780 was able to block E2 action, indicating that the regulation of these genes is ER mediated. The E2 also inhibited the expression and secretion of uPA, tPA and PAI-1 proteins as determined by enzyme-linked immunosorbent assay (ELISA) in cell extracts (CEs) and conditioned media (CM). Zymography of the CM confirmed the inhibitory effect of E2 on uPA activity. Thus, we now report the regulation of uPA, PAI-1 and tPA by E2 in both mRNA and protein levels in ER transfectants. The association between down-regulation of the uPA by E2 and known E2-mediated growth inhibition of these cells was also explored. Our findings indicate that down-regulation of uPA by E2 is an upstream event of inhibitory effects of E2 on growth of these cells as the addition of exogenous uPA did not block the growth inhibition by E2.

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Growth factor-like effect of urokinase type plasminogen activator in human renal cells

Cited by 41 publications

References 13 publications

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Urokinase Plasminogen Activator in Injured Adventitia Increases the Number of Myofibroblasts and Augments Early Proliferation

Oestradiol regulation of the components of the plasminogen-plasmin system in MDA-MB-231 human breast cancer cells stably expressing the oestrogen receptor

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