Involvement of the [uPAR:uPA:PAI-1:LRP] Complex in Human Myogenic Cell Motility

Chazaud, Bénédicte; Bonavaud, Sylvie; Plonquet, Anne; Pouchelet, M.; Gherardi, Romain K.; Barlovatz-Meimon, Georgia

doi:10.1006/excr.2000.4934

Cited by 43 publications

(47 citation statements)

References 45 publications

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“…During migration of several cell types, expression of uPA, uPAR, and PAI-1 is upregulated [Pepper et al, 1993;Andreasen et al, 1997;Chazaud et al, 2000]. Results with many different human cancers have shown that high levels of uPA, uPAR, and PAI-1 in tumors are correlated with poor patient prognosis [Andreasen et al, 1997].…”

Section: Discussionmentioning

confidence: 99%

“…Although the role of LRP in tumor progression remains unclear at the present time, several studies have shown a correlation between LRP expression and human cancer cell invasion and metastasis [Li et al, 1998;Huang et al, 2000]. Under physiological conditions, uPA bound to uPAR catalyzes the conversion of plasminogen to plasmin, which in turn degrades the ECM and facilitates cell migration [Chazaud et al, 2000]. The binding of PAI-1 to uPA inactivates uPA, triggers the recruitment of uPAR by LRP and the formation of a quaternary complex [uPAR Á uPA Á PAI-1 Á LRP] for endocytosis [Chazaud et al, 2000;Czekay et al, 2001].…”

Section: Discussionmentioning

confidence: 99%

“…Under physiological conditions, uPA bound to uPAR catalyzes the conversion of plasminogen to plasmin, which in turn degrades the ECM and facilitates cell migration [Chazaud et al, 2000]. The binding of PAI-1 to uPA inactivates uPA, triggers the recruitment of uPAR by LRP and the formation of a quaternary complex [uPAR Á uPA Á PAI-1 Á LRP] for endocytosis [Chazaud et al, 2000;Czekay et al, 2001]. Subsequently, intracellular degradation of the complex occurs with recycling of uPAR and LRP back to the cell surface [Nykjaer et al, 1997].…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, intracellular degradation of the complex occurs with recycling of uPAR and LRP back to the cell surface [Nykjaer et al, 1997]. Thus, any interference with the [uPAR Á uPA Á PAI-1 Á LRP] complex formation induced a marked decrease in cell migration [Chazaud et al, 2000]. Several lines of evidence suggest that the effects of Dp on U-87 cell migration and invasion involve the uPAR/LRP plasminolytic system.…”

Section: Discussionmentioning

confidence: 99%

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Anthocyanidins inhibit migration of glioblastoma cells: Structure‐activity relationship and involvement of the plasminolytic system

Lamy

Lafleur

Bédard

et al. 2006

J of Cellular Biochemistry

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Complete resection of malignant glioblastomas is usually impossible because of diffuse and widespread invasion of tumor cells, and complementary approaches need to be developed in order to improve the efficacy of current treatments. Consumption of fruits and berries has been associated with decreased risk of developing cancer and there is great interest in the use of molecules from dietary origin to improve anticancer therapies. In this work, we report that the aglycons of the most abundant anthocyanins in fruits, cyanidin (Cy), delphinidin (Dp), and petunidin (Pt), act as potent inhibitors of glioblastoma cell migration. Dp clearly exhibited the highest inhibitory potency, this effect being related to the ortho-dihydroxyphenyl structure on the B-ring and the presence of a free hydroxyl group at position 3. Dp decreases the expression of both urokinase-type plasminogen activator receptor (uPAR) and the low-density lipoprotein receptor-related protein (LRP), acting at the transcriptional levels. In addition, Dp upregulated urokinase-type plasminogen activator (uPA) and downregulated the plasminogen activator inhibitor-1 (PAI-1) but decreased, in a concentration-dependent manner, the uPA-dependent conversion of plasminogen to plasmin, indicating that the upregulation of uPA observed with these compounds was not associated with induction of the plasminolytic activity. Overall, these results demonstrate that Dp, Pt, and Cy affect plasminogen activation, thus leading to the inhibition of glioblastoma cell migration and therefore they may be helpful for the development of new strategies for cancer prevention and therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Anthocyanidins inhibit migration of glioblastoma cells: Structure‐activity relationship and involvement of the plasminolytic system

Lamy

Lafleur

Bédard

et al. 2006

J of Cellular Biochemistry

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“…Interestingly, several of the VHL regulated genes have potential roles in matrix metabolism. LRP1 is a large endocytic receptor that mediates the catabolism of a number of molecules important in vascular biology (Strickland et al, 1995), and appears to play a role in regulation of cell motility (Okada et al, 1996;Chazaud et al, 2000). MIC2/CD99 is a cell surface glycoprotein involved in cell adhesion (Hahn et al, 1997) that is commonly expressed in haematological neoplasms (Soslow et al, 1997;Zhang et al, 2000) and upregulated in Ewing family tumours (Zoubek et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

et al. 2000

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The von Hippel-Lindau tumour suppressor gene (VHL) targets hypoxia inducible factor (HIF)-a subunits for ubiquitin dependent proteolysis. To better understand the role of this and other putative pathways of gene regulation in VHL function we subjected mRNA from VHL defective renal carcinoma cells and transfectants re-expressing a wild type VHL allele to di erential expression pro®ling, and analysed VHL target genes for oxygen regulated expression. Among a group of newly identi®ed VHL target genes the majority but not all were regulated by oxygen, indicating that whilst dysregulation of the HIF system makes a dominant contribution to alterations in transcription, VHL has other in¯uences on patterns of gene expression. Genes newly de®ned as targets of the VHL/hypoxia pathway (conditionally downregulated by VHL in normoxic cells) include aminopeptidase A, collagen type V, alpha 1, cyclin G2, DEC1/Stra13, endothelin 1, low density lipoprotein receptor-related protein 1, MIC2/CD99, and transglutaminase 2. These genes have a variety of functions relevant to tumour biology. However, not all are connected with the promotion of tumour growth, some being pro-apoptotic or growth inhibitory. We postulate that co-ordinate regulation as part of the HIF pathway may explain this paradox, and that evolution of antiapoptotic pathways may be required for tumour growth under VHL-dysregulation. Our results indicate that it will be necessary to consider the e ects of abnormal activity in integral regulatory pathways, as well as the e ects of individual genes to understand the role of abnormal patterns of gene expression in cancer. Oncogene (2000) 19, 6297 ± 6305.

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Urokinase type plasminogen activator receptor is involved in insulin‐like growth factor‐induced migration of rhabdomyosarcoma cells in vitro

Gallicchio

Kaun

Wojta

et al. 2003

Journal Cellular Physiology

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Urokinase-type plasminogen activator (uPA) binds to its receptor, uPAR, on the surface of cancer cells, leading to the formation of plasmin. Rhabdomyosarcoma (RMS) cell lines secrete high levels of insulin-like growth factor II (IGF-II), suggesting autocrine IGFs play a major role in the unregulated growth and metastasis of RMS. In vitro, IGF-II and IGF-I increased migration of RD cells to 124+/-9% (P<0.01) and 131+/-8% (P<0.05) of control, respectively. IGF-II-induced migration was abolished by insulin-like growth factor binding protein-6 (IGFBP-6) (P<0.01), a relatively specific inhibitor of IGF-II, and by plasminogen activator inhibitor type 1 (PAI-1) (P<0.05). Aprotinin, a plasmin inhibitor, and mannosamine, which inhibits the synthesis of glycosylphosphatidylinositol (GPI), thereby preventing anchorage of GPI-linked proteins such as uPAR to the cell membrane, also decreased IGF-II- (P<0.05 for both) but not IGF-I-induced migration. [Arg54,Arg55]IGF-II and [Leu27]IGF-II, which preferentially bind to the IGF-I and IGF-II/mannose-6-phosphate receptors (IGF-II/M6PR), respectively, both induced RD cell migration to 146+/-8% (P<0.01) and 120+/-7% (P<0.05) of control, respectively. An anti-uPAR anti-serum reduced IGF-II- and IGF-I-induced migration (P<0.05 for both). An anti-low density lipoprotein-related protein (LRP) anti-serum reduced IGF-I-induced migration (P<0.05). IGF-I and -II both increased specific 125I-single chain uPA (scuPA) binding to RD cells in a dose-dependent manner (P<0.01). These results suggest involvement of the PA/plasmin system in IGF-induced migration and indicate important roles these systems may have in RMS metastasis.

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Involvement of the [uPAR:uPA:PAI-1:LRP] Complex in Human Myogenic Cell Motility

Cited by 43 publications

References 45 publications

Anthocyanidins inhibit migration of glioblastoma cells: Structure‐activity relationship and involvement of the plasminolytic system

Anthocyanidins inhibit migration of glioblastoma cells: Structure‐activity relationship and involvement of the plasminolytic system

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

Urokinase type plasminogen activator receptor is involved in insulin‐like growth factor‐induced migration of rhabdomyosarcoma cells in vitro

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