In vitro Invasiveness of Human Breast Cancer Cells Is Promoted by Low Density Lipoprotein Receptor-Related Protein

1998 ◽  
Vol 18 (5-6) ◽  
pp. 240-251 ◽  
Author(s):  
Yonghe Li ◽  
Nick Wood ◽  
Philip Grimsley ◽  
David Yellowlees ◽  
Peter K. Donnelly
Keyword(s):  
Breast Cancer Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Receptor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Density Lipoprotein Receptor ◽  
In Vitro Invasiveness ◽  
Lipoprotein Receptor Related Protein

A Novel Low-Density Lipoprotein Receptor-Related Protein Mediating Cellular Uptake of Apolipoprotein E-Enriched β-VLDL in Vitro†,‡

Biochemistry ◽  
2000 ◽  
Vol 39 (51) ◽  
pp. 15817-15825 ◽  
Author(s):  
Takuya Sugiyama ◽  
Hidetoshi Kumagai ◽  
Yoshihiro Morikawa ◽  
Yoichiro Wada ◽  
Akira Sugiyama ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Cellular Uptake ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Related Protein ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein

scholarly journals Recombinant Tissue Plasminogen Activator (r-tPA) Induces In-Vitro Human Neutrophil Migration via Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1)

2020 ◽  
Vol 21 (19) ◽  
pp. 7014
Author(s):  
Luca Liberale ◽  
Maria Bertolotto ◽  
Silvia Minetti ◽  
Paola Contini ◽  
Daniela Verzola ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Neutrophil Migration ◽  
Density Lipoprotein ◽  
Recombinant Tissue Plasminogen Activator ◽  
Lipoprotein Receptor ◽  
Related Protein ◽  
Tissue Plasminogen ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein

Thrombolysis is the gold standard treatment for acute ischemic stroke. Besides its fibrinolytic role, recombinant tissue plasminogen activator (r-tPA) holds several non-fibrinolytic functions. Here, we investigated the potential role of r-tPA on human primary neutrophil migration in vitro. By means of modified Boyden chamber migration assay and checkerboard analysis we showed a dose-dependent chemotactic effect of r-TPA with a maximum effect reached by 0.03 mg/mL (0.003–1 mg/mL). Pre-incubation with MAP kinases inhibitors allowed the identification of PI3K/Akt, but not ERK1/2 as the intracellular pathway mediating the observed effects. Furthermore, by means of real-time PCR, immunocytochemistry and cytofluorimetry we demonstrated that the r-tPA receptor low density lipoprotein receptor-related protein 1 (LRP-1) is synthetized and expressed by neutrophils in response to r-tPA and TNF-α. Inhibition of LRP-1 by receptor-associated protein (RAP), prevented r-tPA-mediated F-actin polymerization, migration and signal through Akt but not ERK1/2. Lastly, also neutrophil degranulation in response to r-tPA seems to be mediated by LRP-1 under adhesion conditions. In conclusion, we show that r-tPA induces neutrophil chemotaxis through LRP-1/Akt pathway. Blunting r-tPA-mediated neutrophil activation might be beneficial as an adjuvant therapy to thrombolysis in this setting.

scholarly journals The low-density-lipoprotein receptor-related protein (LRP) is processed by furin in vivo and in vitro

1996 ◽  
Vol 313 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Thomas E. WILLNOW ◽  
Joan M. MOEHRING ◽  
Noel M. INOCENCIO ◽  
Thomas J. MOEHRING ◽  
Joachim HERZ
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Proteolytic Processing ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Related Protein ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein

The low-density-lipoprotein receptor-related protein (LRP) is a multifunctional receptor involved in the clearance of a large number of diverse ligands, including proteases, protease-inhibitor complexes and lipoproteins. The mature receptor is composed of a 515 kDa and a 85 kDa subunit generated by proteolytic cleavage from a 600 kDa precursor polypeptide in a trans-Golgi compartment. Proteolytic processing occurs C-terminal to the tetrabasic amino acid sequence RHRR, a consensus recognition site for precursor processing endoproteases or convertases. In this study we have identified furin, a subtilisin-type protease, to be necessary for efficient processing of LRP in cells. Furin-deficient RPE.40 cells exhibited an impaired processing of endogenous LRP and of a recombinant soluble form of the receptor containing the processing site. The processing defect in RPE.40 cells could be complemented by expression of furin from a transfected cDNA in cultured cells and by purified furin in vitro. The impaired maturation of LRP in RPE.40 cells did not affect its intracellular transport, and correlated with a slight but consistent reduction in the endocytosis of LRP-specific ligands. These data suggest that proteolytic processing of LRP by furin is not necessary for intracellular trafficking but might be required for normal receptor activity.

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