PAR-1- and PAR-3-type thrombin receptor expression in primary cultures of human renal cell carcinoma cells

Kaufmann, Roland; Junker, Uwe; Nuske, K.; Westermann, Martin; Henklein, Peter; Scheele, J.; Junker, Kerstin

doi:10.3892/ijo.20.1.177

Cited by 18 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From the size relationship, proteins with only one or two transmembrane segments would not be visible as intramembranous particles. Large receptors are also visible as intramembranous particles (e.g., Cohen and Pumplin, 1979;Pumplin and Drachman, 1983;Kaufmann et al, 2002), as are the sodium channels of neurons and the sodium-potassium ATPase (Pumplin and Fambrough, 1983). Taken together, the results suggest: 1) that IMP in olfactory nerves may represent ion channels, ion pumps, or other large, multi-helix proteins; and 2) that IMPs are all aligned in membranes facing the small longitudinal columns of extracellular fluid that separate the axons.…”

Section: Discussionmentioning

confidence: 60%

Intercellular interactions in the mammalian olfactory nerve

Blinder

Pumplin

Paul

et al. 2003

J of Comparative Neurology

View full text Add to dashboard Cite

The small, unmyelinated axons of olfactory sensory neurons project to the olfactory bulb in densely packed fascicles, an arrangement conducive to axo-axonal interactions. We recently demonstrated ephaptic interactions between these axons in the olfactory nerve layer, the layer of the olfactory bulb in which the axon fascicles interweave and rearrange extensively. In the present study, we hypothesized that the axons, which express connexins, may have another mode of communication: gap junctions. Previous transmission electron microscopy (TEM) studies have failed to demonstrate such junctions. However, the definitive method for detecting gap junctions, freeze fracture, has not been used to examine the interaxonal connections of the olfactory nerve layer. Here, we apply a combined approach of TEM and freeze fracture to determine if gap junctions are present between the olfactory axons. Gap junctions involving olfactory axons were not found. However, by freeze fracture, P faces of both the axons and ensheathing cells (glia that surround the axon fascicles) contained distinctive linear arrays of particles, aligned along the small columns of extracellular space. In axons, few intramembranous particles were present outside of these arrays. Multi-helix proteins, including ion channels and connexin hemichannels, have been shown to be visible as particles by freeze fracture. This suggests that the proteins important for signal transmission are confined to the linear arrays. Such an arrangement would facilitate ephaptic transmission, calcium waves, current oscillations, and paracrine communication and may be important for olfactory neural code processing.Keywords freeze fracture; ultrastructure; olfactory bulb; ephaptic; connexins; hemichannels Olfactory receptor neurons project from the olfactory epithelium to the olfactory bulb by dense bundles of thin, unmyelinated olfactory axons (Marin-Padilla and Amieva, 1989;Daston et al., 1990;Mori, 1993). The high packing density of these axons and the absence of intervening glia suggest that olfactory coding may be affected by axoaxonal interactions.We recently demonstrated (Bokil et al., 2001) that neighboring axons are able to influence each other by ephaptic interactions-current spread through the small extracellular space. We have argued (Bokil et al., 2001) that ephaptic interactions, as well as interneuronal interactions mediated by extruded potassium ions (Bliss and Rosenberg, 1979) First, olfactory receptors of mature mammals are constantly regenerated (Graziadei and Graziadei, 1979;Graziadei and Monti Graziadei, 1983), and developing neurons of the central nervous system are often extensively coupled by gap junctions (reviewed in Kandler and Katz, 1995;Naus and Bani-Yaghoub, 1998;Chang and Balice-Gordon, 2000). Second, olfactory receptor neurons express connexins, the proteins that form gap junctions. Olfactory receptor neurons express mRNA for connexins 43 (Zhang et al., 2000), 45 (Zhang andRestrepo, 2002), and 36 (Zhang andRestrepo, 2003). Furthermore, in immun...

show abstract

Section: Discussionmentioning

confidence: 60%

Intercellular interactions in the mammalian olfactory nerve

Blinder

Pumplin

Paul

et al. 2003

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…The difference of thrombin and SFLLRN on MMPs activities demonstrated other signaling pathway must be responsible for thrombin function in NPC cells. Besides PAR-1, there are other thrombin receptors on cell membrane of many types cells, and thrombin might exert its effect through these receptors (16,49).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that PAR-1 was expressed highly in many types of cancer, such as breast cancer (9), malignant melanoma (10), prostate cancer (11), colon cancer (12), lung cancer (13), oral squamous cell carcinoma (14), esophageal cancer (15), and renal cell carcinoma (16). Early study by Even-Ram et al (9) demonstrated that PAR-1 expression levels were correlated with degree of invasiveness in both primary breast tissue specimens and established cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

et al. 2012

View full text Add to dashboard Cite

Abstract. Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein, which is involved in physiological and malignant invasion processes. It is activated by serine proteases such as thrombin through a unique form or by specific synthetic peptides. In this study, we determined the expression of PAR-1 in five nasopharyngeal carcinoma (NPC) cell lines with different characteristics of invasiveness and metastasis, and found that the levels of PAR-1 expression were higher in invasive or metastatic cell lines than those in low invasive or metastatic ones. Of the five NPC cell lines, CNE1-LMP1 cells had the highest expression levels of PAR-1, which was mainly distributed at the membrane and in the cytoplasm of tumor cells. Further study showed that the thrombin receptor synthetic activating peptide SFLLRN could stimulate the growth of CNE1-LMP1 cells in a dosedependent manner. However, thrombin itself had a dual effect on the proliferation of NPC cells. Concentrations of thrombin in the range of 0.1-0.5 U/ml promoted cell growth, but concentrations higher than 0.5 U/ml impaired cell growth. Moreover, thrombin and SFLLRN also enhanced the invasive capabilities of CNE1-LMP1 cells in vitro, and this was partly due to enhancing the activities of MMP-2 and MMP-9. Our findings suggest that PAR-1 may contribute to the growth and invasive potential of NPC cells.

show abstract

“…Primary cultures, PHC1 and PHC2, were established from surgically resected specimens of primary hepatocellular carcinomas from patients who underwent surgery in the Department of General, Visceral and Vascular Surgery as described (34). To confirm their epithelial nature and to exclude myofibroblast contam-ination, cell cultures were analyzed by a standard immunochemistry approach, using a monoclonal anticytokeratin antibody (DacoCytomation GmbH, Germany, clone MNF116) and an anti-smooth muscle actin antibody (DacoCytomation GmbH, clone 1A4).…”

Section: Reagentsmentioning

confidence: 99%

Green tea polyphenol epigallocatechin-3-gallate inhibits thrombin-induced hepatocellular carcinoma cell invasion and p42/p44-MAPKinase activation

Kaufmann

Henklein²,

Henklein³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract.Thrombin has been recently demonstrated to promote hepatocellular carcinoma (HCC) cell migration by activation of the proteinase-activated receptor (PAR) subtypes PAR 1 and PAR 4 suggesting a role of these proteinasereceptor systems in HCC progression. In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic compound of green tea on thrombin-PAR 1 /PAR 4 -mediated hepatocellular carcinoma cell invasion and p42/p44 MAPKinase activation. In this study we used the permanent liver carcinoma cell line HEP-3B and two primary cultures established from surgically resected HCCs. We found that stimulation of HCC cells with thrombin, the PAR 1 -selective activating peptide, TFLLRN-NH 2 , and the PAR 4 -selective activating peptide, AYPGKF-NH 2 , increased cell invasion across a Matrigel-coated membrane barrier and stimulated activation of p42/p44 MAPKinase phosphorylation. Both the effects on p42/p44 MAPKinases, and on cell invasiveness induced by thrombin and the PAR 1/4 subtype-selective agonist peptides were effectively blocked by EGCG. The results clearly identify EGCG as a potent inhibitor of the thrombin-PAR 1 /PAR 4 -p42/p44 MAPKinase invasive signaling axis in hepatocellular carcinoma cells as a previously unrecognized mode of action for EGCG in cancer cells. Moreover, the results suggest that (-)-epigal-locatechin-3-gallate might have therapeutic potential for hepatocellular carcinoma.

show abstract

PAR-1- and PAR-3-type thrombin receptor expression in primary cultures of human renal cell carcinoma cells

Cited by 18 publications

References 18 publications

Intercellular interactions in the mammalian olfactory nerve

Intercellular interactions in the mammalian olfactory nerve

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

Green tea polyphenol epigallocatechin-3-gallate inhibits thrombin-induced hepatocellular carcinoma cell invasion and p42/p44-MAPKinase activation

Contact Info

Product

Resources

About